Dosing Strategy of Ramosetron to Prevent Postoperative Nausea and Vomiting and Development of Prediction Models Using Data Obtained From Randomized Controlled Trials: A Comparative Study.

PURPOSE: The study aimed to compare the postoperative nausea and vomiting (PONV) preventive effect of repeated administration of ramosetron with the standard treatment group and compare models to predict the incidence of PONV using machine-learning techniques. METHODS: A total of 261 patients scheduled for breast surgery were analyzed to evaluate the effectiveness of repeated intravenous administration of ramosetron. All patients were administered 0.3 mg ramosetron just before the end of surgery. For the repeated dose of ramosetron group, an additional dose of 0.3 mg was administered at 4, 22, and 46 hours after the end of the surgery. Postoperative nausea, vomiting, and retching were evaluated using the Rhodes Index of Nausea, Vomiting, and Retching at 6, 24, and 48 hours postoperatively. Previously published randomized controlled data were combined with the data of this study to create a new dataset of 1390 patients, and machine-learning-based PONV prediction models (classification tree, random forest, extreme gradient boosting, and neural network) was constructed and compared with the Apfel model. FINDINGS: Fifty patients (38.5%) and 60 patients (45.8%) reported nausea, vomiting, or retching 48 hours postoperatively in the standard and repeated-dose groups, respectively (P = 0.317, χ2 test). Median sensitivity, specificity, and accuracy of the Apfel model analyzed using the training set were 0.815, 0.344, and 0.495, respectively. IMPLICATIONS: The repeated administration of ramosetron did not reduce the incidence of PONV. The Apfel model had high sensitivity, however, its specificity and accuracy were lower than that in machine-learning-based models.

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.

Disparities in Preoperative Goals of Care Documentation in Veterans.

Importance: Preoperative goals of care discussion and documentation are important for patients undergoing surgery, a major health care stressor that incurs risk. Objective: To assess the association of race, ethnicity, and other factors, including history of mental health disability, with disparities in preoperative goals of care documentation among veterans. Design, Setting, and Participants: This retrospective cross-sectional study assessed data from the Veterans Healthcare Administration (VHA) of 229 737 veterans who underwent surgical procedures between January 1, 2017, and October 18, 2022. Exposures: Patient-level (ie, race, ethnicity, medical comorbidities, history of mental health comorbidity) and system-level (ie, facility complexity level) factors. Main Outcomes and Measures: Preoperative life-sustaining treatment (LST) note documentation or no LST note documentation within 30 days prior to or on day of surgery. The standardized mean differences were calculated to assess the magnitude of differences between groups. Odds ratios (ORs) and 95% CIs were estimated with logistic regression. Results: In this study, 13 408 patients (5.8%) completed preoperative LST from 229 737 VHA patients (209 123 [91.0%] male; 20 614 [9.0%] female; mean [SD] age, 65.5 [11.9] years) who received surgery. Compared with patients who did complete preoperative LST, patients tended to complete preoperative documentation less often if they were female (19 914 [9.2%] vs 700 [5.2%]), Black individuals (42 571 [19.7%] vs 2416 [18.0%]), Hispanic individuals (11 793 [5.5%] vs 631 [4.7%]), or from rural areas (75 637 [35.0%] vs 4273 [31.9%]); had a history of mental health disability (65 974 [30.5%] vs 4053 [30.2%]); or were seen at lowest-complexity (ie, level 3) facilities (7849 [3.6%] vs 78 [0.6%]). Over time, despite the COVID-19 pandemic, patients undergoing surgical procedures completed preoperative LST increasingly more often. Covariate-adjusted estimates of preoperative LST completion demonstrated that patients of racial or ethnic minority background (Black patients: OR, 0.79; 95% CI, 0.77-0.80; P <.001; patients selecting other race: OR, 0.78; 95% CI, 0.74-0.81; P <.001; Hispanic patients: OR, 0.78; 95% CI, 0.76-0.81; P <.001) and patients from rural regions (OR, 0.91; 95% CI, 0.90-0.93; P <.001) had lower likelihoods of completing LST compared with patients who were White or non-Hispanic and patients from urban areas. Patients with any mental health disability history also had lower likelihood of completing preoperative LST than those without a history (OR, 0.93; 95% CI, 0.92-0.94; P = .001). Conclusions and Relevance: In this cross-sectional study, disparities in documentation rates within a VHA cohort persisted based on race, ethnicity, rurality of patient residence, history of mental health disability, and access to high-volume, high-complexity facilities.

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.

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 ).

Frequency and characteristics of patients with bispectral index values of 60 or higher during the induction and maintenance of general anesthesia with remimazolam.

In Korea, the approved anesthetic regimen of remimazolam starts with 6 mg/kg/h or 12 mg/kg/h until loss of consciousness, followed by maintenance at 1-2 mg/kg/h. Some patients receiving remimazolam for general anesthesia experience occasional difficulty maintaining bispectral index (BIS) value ˂ 60. This retrospective study aimed to analyze the data from patients undergoing elective surgery under remimazolam based-general anesthesia to determine the frequency and physical characteristics of patients with BIS values ˂ 60. The criterion was established for patients with a poorly maintained BIS value < 60. The frequency and physical characteristics of patients who satisfied this criterion were investigated through their medical records. The modified Brice interview was conducted within 24 h after surgery. Among the 1500 patients included in the analysis, 61 (4.1%) met the criteria for BIS ˂ 60. Based on the modified Brice interview, none of the patients with poorly maintained BIS ˂ 60 complained of intraoperative awareness based on the modified Brice interview or exhibit specific physical characteristics. These patients accounted for less than 5% of the total population studied. Notably, physical characteristics alone are insufficient to predict such patients before surgery.

Patient Characteristics Associated With Occurrence of Preoperative Goals-of-Care Conversations.

Importance: Communication about patients' goals and planned and potential treatment is central to advance care planning. Undertaking or confirming advance care plans is also essential to preoperative preparation, particularly among patients who are frail or will undergo high-risk surgery. Objective: To evaluate the association between patient risk of hospitalization or death and goals-of-care conversations documented with a completed Life-Sustaining Treatment (LST) Decisions Initiative note among veterans undergoing surgery. Design, Setting, and Participants: This retrospective cross-sectional study included 190 040 veterans who underwent operations between January 1, 2017, and February 28, 2020. Statistical analysis took place from November 1, 2021, to November 17, 2022. Exposure: Patient risk of hospitalization or death, evaluated with a Care Assessment Need (CAN) score (range, 0-99, with a higher score representing a greater risk of hospitalization or death), dichotomized as less than 80 or 80 or more. Main Outcomes and Measures: Preoperative LST note completion (30 days before or on the day of surgery) or no LST note completion within the 30-day preoperative period prior to or on the day of the index operation. Results: Of 190 040 veterans (90.8% men; mean [SD] age, 65.2 [11.9] years), 3.8% completed an LST note before surgery, and 96.2% did not complete an LST note. In the groups with and without LST note completion before surgery, most were aged between 65 and 84 years (62.1% vs 56.7%), male (94.3% vs 90.7%), and White (82.2% vs 78.3%). Compared with patients who completed an LST note before surgery, patients who did not complete an LST note before surgery tended to be female (9.3% vs 5.7%), Black (19.2% vs 15.7%), married (50.2% vs 46.5%), and in better health (Charlson Comorbidity Index score of 0, 25.9% vs 15.2%); to have a lower risk of hospitalization or death (CAN score <80, 98.3% vs 96.9%); or to undergo neurosurgical (9.8% vs 6.2%) or urologic surgical procedures (5.9% vs 2.0%). Over the 3-year interval, unadjusted rates of LST note completion before surgery increased from 0.1% to 9.6%. Covariate-adjusted estimates of LST note completion indicated that veterans at a relatively elevated risk of hospitalization or death (CAN score ≥80) had higher odds of completing an LST note before surgery (odds ratio [OR], 1.29; 95% CI, 1.09-1.53) compared with those with CAN scores less than 80. High-risk surgery was not associated with increased LST note completion before surgery (OR, 0.93; 95% CI, 0.86-1.01). Veterans who underwent cardiothoracic surgery had the highest likelihood of LST note completion before surgery (OR, 1.35; 95% CI, 1.24-1.47). Conclusions and Relevance: Despite increasing LST note implementation, a minority of veterans completed an LST note preoperatively. Although doing so was more common among veterans with an elevated risk compared with those at lower risk, improving proactive communication and documentation of goals, particularly among higher-risk veterans, is needed. Doing so may promote goal-concordant surgical care and outcomes.

Racial disparities in inpatient palliative care consultation among frail older patients undergoing high-risk elective surgical procedures in the United States: a cross-sectional study of the national inpatient sample.

Surgical interventions are common among seriously ill older patients, with nearly one-third of older Americans facing surgery in their last year of life. Despite the potential benefits of palliative care among older surgical patients undergoing high-risk surgical procedures, palliative care in this population is underutilized and little is known about potential disparities by race/ethnicity and how frailty my affect such disparities. The aim of this study was to examine disparities in palliative care consultations by race/ethnicity and assess whether patients' frailty moderated this association. Drawing on a retrospective cross-sectional study of inpatient surgical episodes using the National Inpatient Sample of the Healthcare Cost and Utilization Project from 2005 to 2019, we found that frail Black patients received palliative care consultations least often, with the largest between-group adjusted difference represented by Black-Asian/Pacific Islander frail patients of 1.6 percentage points, controlling for sociodemographic, comorbidities, hospital characteristics, procedure type, and year. No racial/ethnic difference in the receipt of palliative care consultations was observed among nonfrail patients. These findings suggest that, in order to improve racial/ethnic disparities in frail older patients undergoing high-risk surgical procedures, palliative care consultations should be included as the standard of care in clinical care guidelines.

Comparison of the C-MAC D-blade video laryngoscope and the McCoy laryngoscope for double-lumen endotracheal tube intubation: A prospective randomized controlled study.

BACKGROUND: Inserting a double-lumen endotracheal tube (DLT) poses more challenge than inserting a single-lumen tube. The C-MAC D-blade videolaryngoscope is a useful alternative to the direct laryngoscope. However, no study has compared its performance with that of the McCoy laryngoscope, which has a hyperangulated blade tip similar to that of the C-MAC D-blade. We aimed to compare the performance of the C-MAC D-blade videolaryngoscope with that of the McCoy laryngoscope in DLT intubation. METHODS: In this prospective randomized controlled study, 90 patients requiring DLT intubation were randomly allocated to either the C-MAC D-blade videolaryngoscope group (group C, n = 47) or McCoy laryngoscope group (group M, n = 43). During intubation, the percentage of glottic opening, modified Cormack-Lehane grade, time taken for intubation, malposition of the bronchial lumen, and hemodynamic parameters were recorded. After intubation, we assessed the intubation difficulty scale score and, a postoperative sore throat in the recovery room. RESULTS: The time taken for intubation was 35.85 ±â€…10.77 seconds and 33.18 ±â€…11.97 seconds in groups C and M, respectively (P = .269). The modified Cormack-Lehane grade was significantly lower in group C than in group M (P = .000). Percentage of glottic opening was significantly higher in group C (79.36 ±â€…13.42%) than in group M (53.49 ±â€…29.83%) (P = .000). The intubation difficulty scale score was significantly lower in group C than in group M (P = .030). There were no significant differences between the 2 groups in terms of malposition status, hemodynamic parameters, or visual analog scale score for a postoperative sore throat. CONCLUSION: Although the time taken for intubation was comparable between the 2 intubation devices, the C-MAC D-blade videolaryngoscope facilitated glottis visualization and reduced the intubation difficulty scale better than the McCoy laryngoscope in patients undergoing DLT intubation.

Effect-site concentration of remimazolam at loss and recovery of responsiveness during general anesthesia: a simulation study.

BACKGROUND: The objective of this study was to investigate the effect-site concentration (Ce) of remimazolam at loss of response (LOR) and recovery of response (ROR) in patients underwent general anesthesia using simulation. In addition, the relationships between patient's factors and simulated Ce at LOR and ROR were examined. METHODS: The medical records of 81 patients who underwent elective surgery under general anesthesia using remimazolam with simulation of Ce between August 4, 2021 and October 12, 2021, were retrospectively reviewed. Remimazolam was administered as an induction dose of 6 or 12 mg/kg/h until the patient became unresponsive, followed by 0.3-2 mg/kg/ h to maintain BIS values below 60. Simultaneously, simulations of manual infusion mode were performed using Asan Pump software and the Ce of remimazolam was simulated using the Schüttler model. Whenever infusion rate of remimazolam was manually changed, the simulated Ce was confirmed almost simultaneously. LOR and ROR, defined as unresponsive and eye-opening to verbal commands, respectively, were recorded in the Asan Pump program. RESULTS: The median (1Q, 3Q) simulated Ce at LOR and ROR were 0.7 (0.5, 0.9) and 0.3 (0.2, 0.4) µg/ml, respectively. LOR was achieved in 1.9 min after remimazolam infusion with cumulative doses of 0.3 mg/kg. There was a significant relationship between age and simulated Ce at ROR (Ce at ROR = -0.0043 × age + 0.57, r = 0.30, P = 0.014). CONCLUSIONS: For optimal dosage adjustment, simulating Ce while administering remimazolam with a weight-based dose during anesthesia is helpful. Elderly patients may recover from anesthesia at lower Ce of remimazolam.

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.

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.

Mothers of children with major congenital anomalies have increased health care utilization over a 20-year post-birth time horizon.

OBJECTIVE: This population-based, matched cohort study aimed to evaluate utilization of health care services by mothers of children with major congenital anomalies (MCAs), compared to mothers of children without MCAs over a 20-year post-birth time horizon in Denmark. METHODS: Our analytic sample included mothers who gave birth to an infant with a MCA (n = 23,927) and a cohort of mothers matched to them by maternal age, parity and infant's year of birth (n = 239,076). Primary outcomes were period prevalence and mothers' quantity of health care utilization (primary, inpatient, outpatient, surgical, and psychiatric services) stratified by their child's age (i.e., ages 0-6 = before school, ages 7-13 = pre-school + primary education, and ages 14-18 = secondary education or higher). The secondary outcome measure was length of hospital stays. Outcome measures were adjusted for maternal age at delivery, parity, marital status, income quartile, level of education in the year prior to the index birth, previous spontaneous abortions, maternal pregnancy complications, maternal diabetes, hypertension, alcohol-related diseases, and maternal smoking. RESULTS: In both cohorts the majority of mothers were between 26 and 35 years of age, married, and employed, and 47% were primiparous. Mothers of infants with anomalies had greater utilization of outpatient, inpatient, surgical, and psychiatric services, compared with mothers in the matched cohort. Inpatient service utilization was greater in the exposed cohort up to 13 years after a child's birth, with the highest risk in the first six years after birth [adjusted risk ratio, 1.13; 95% confidence interval (CI), 1.12-1.14], with a decrease over time. Regarding the quantity of health care utilization, the greatest difference between the two groups was in inpatient service utilization, with a 39% increased rate in the exposed cohort during the first six years after birth (adjusted rate ratio, 1.39; 95% CI, 1.37-1.42). During the first 6 years after birth, mothers of children with anomalies stayed a median of 6 days (interquartile range [IQR], 3-13) in hospital overall, while the comparison cohort stayed a median of 4 days (IQR, 2-7) in hospital overall. Rates of utilization of outpatient clinics (adjusted rate ratio, 1.36; 95% CI, 1.29-1.42), as well as inpatient (adjusted rate ratio, 1.77; 95% CI, 1.68-1.87), and surgical services (adjusted rate ratio, 1.33; 95% CI, 1.26-1.41) was higher in mothers of children with multiple-organ MCAs during 0 to 6 years after birth. Among mothers at the lowest income levels, utilization of psychiatric clinic services increased to 59% and when their child was 7 to 13 years of age (adjusted rate ratio, 1.59; 95% CI, 1.24-2.03). CONCLUSION: Mothers of infants with a major congenital anomaly had greater health care utilization across services. Health care utilization decreased over time or remained stable for outpatient, inpatient, and surgical care services, whereas psychiatric utilization increased for up to 13 years after an affected child's birth. Healthcare utilization was significantly elevated among mothers of children with multiple MCAs and among those at the lowest income levels.

Evaluation of Clinical and Economic Outcomes Following Implementation of a Medicare Pay-for-Performance Program for Surgical Procedures.

Importance: Surgical complications increase hospital costs by approximately $20 000 per admission and extend hospital stays by 9.7 days. Improving surgical care quality and reducing costs is needed for patients undergoing surgery, health care professionals, hospitals, and payers. Objective: To evaluate the association of the Hospital-Acquired Conditions Present on Admission (HAC-POA) program, a mandated national pay-for-performance program by the Centers for Medicare & Medicaid Services, with surgical care quality and costs. Design, Setting, and Participants: A cross-sectional study of Medicare inpatient surgical care stays from October 2004 through September 2017 in the US was conducted. The National Inpatient Sample and a propensity score-weighted difference-in-differences analysis of hospital stays with associated primary surgical procedures was used to compare changes in outcomes for the intervention and control procedures before and after HAC-POA program implementation. The sample consisted of 1 317 262 inpatient surgical episodes representing 1 198 665 stays for targeted procedures and 118 597 stays for nontargeted procedures. Analyses were performed between November 1, 2020, and May 7, 2021. Exposures: Implementation of the HAC-POA program for the intervention procedures included in this study (fiscal year 2009). Main Outcomes and Measures: Incidence of surgical site infections and deep vein thrombosis, length of stay, in-hospital mortality, and hospital costs. Analyses were adjusted for patient and hospital characteristics and indicators for procedure type, hospital, and year. Results: In our propensity score-weighted sample, the intervention procedures group comprised 1 047 351 (88.5%) individuals who were White and 742 734 (60.6%) women; mean (SD) age was 75 (6.9) years. The control procedures group included 94 715 (88.0%) individuals who were White, and 65 436 (60.6%) women; mean (SD) age was 75 (7.1) years. After HAC-POA implementation, the incidence of surgical site infections in targeted procedures decreased by 0.3 percentage points (95% CI, -0.5 to -0.1 percentage points; P = .02) compared with nontargeted procedures. The program was associated with a reduction in length of stay by 0.5 days (95% CI, -0.6 to -0.4 days; P < .001) and hospital costs by 8.1% (95% CI, -10.2% to -6.1%; P < .001). No significant changes in deep vein thrombosis incidence and mortality were noted. Conclusions and Relevance: The findings of this study suggest that the HAC-POA program is associated with small decreases in surgical site infection and length of stay and moderate decreases in hospital costs for patients enrolled in Medicare. Policy makers may consider these findings when evaluating the continuation and expansion of this program for other surgical procedures, and payers may want to consider adopting a similar policy.

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.

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 penalty-based pay-for-performance programs improve surgical care more effectively than other payment strategies? A systematic review.

BACKGROUND: The aim of this systematic review is to assess if penalty-based pay-for-performance (P4P) programs are more effective in improving quality and cost outcomes compared to two other payment strategies (i.e., rewards and a combination of rewards and penalties) for surgical care in the United States. Penalty-based programs have gained in popularity because of their potential to motivate behavioral change more effectively than reward-based programs to improve quality of care. However, little is known about whether penalties are more effective than other strategies. MATERIALS AND METHODS: A systematic literature review was conducted according to the PRISMA guideline to identify studies that evaluated the effects of P4P programs on quality and cost outcomes for surgical care. Five databases were used to search studies published from 2003 to March 1, 2020. Studies were selected based on the PRISMA guidelines. Methodological quality of individual studies was assessed based on ROBINS-I with GRADE approach. RESULTS: This review included 22 studies. Fifteen cross-sectional, 1 prospective cohort, 4 retrospective cohort, and 2 case-control studies were found. We identified 11 unique P4P programs: 5 used rewards, 3 used penalties, and 3 used a combination of rewards and penalties as a payment strategy. Five out of 10 studies reported positive effects of penalty-based programs, whereas evidence from studies evaluating P4P programs with a reward design or combination of rewards and penalties was little or null. CONCLUSIONS: This review highlights that P4P programs with a penalty design could be more effective than programs using rewards or a combination of rewards and penalties to improve quality of surgical care.

Protective role of fermented mulberry leave extract in LPS­induced inflammation and autophagy of RAW264.7 macrophage cells.

Mulberry leaves have antioxidant activity and anti­inflammatory effects in several types of cells. However, the efficacy of mulberry leaves fermented with Cordyceps militaris remains unknown. Therefore, the present study aimed to investigate whether the ethanol extracts of mulberry leaves fermented with C. militaris (EMfC) can prevent lipopolysaccharide (LPS)­induced inflammation and autophagy in macrophages. To achieve this, RAW264.7 cells pretreated with three different dose of EMfCs were subsequently stimulated with LPS, and examined for alterations in the regulatory factors of inflammatory responses and key parameters of the autophagy signaling pathway. EMfC treatment inhibited the generation of reactive oxidative species; however, significant activity was observed for 2,2­diphenyl­1­picrylhydrazyl (DPPH) radical scavenging (IC50=579.6703 mg/ml). Most regulatory factors in inflammatory responses were significantly inhibited following treatment with EMfC, without any significant cellular toxicity. EMfC­treated groups exhibited marked suppression of nitrogen oxide (NO) levels, mRNA expression levels of iNOS/COX­2, levels of all inflammatory cytokines (TNF­α, IL­1ß and IL­6) and phosphorylation of MAPK members, as well as recovery of cell cycle progression. Furthermore, similar effects were observed in the LPS­induced autophagy signaling pathway of RAW264.7 cells. The expression levels of microtubule­associated protein 1A/1B­light chain 3 (LC3) and Beclin exhibited a dose­dependent decrease in the EMfC+LPS­treated groups compared with in the Vehicle+LPS­treated group, whereas the phosphorylation of PI3K and mTOR were enhanced in a dose­dependent manner in the same groups. Overall, the results of the present study provide evidence that exposure to EMfC protects against LPS­induced inflammation and autophagy in RAW264.7 cells. These results indicated that EMfC is a potential candidate for treatment of inflammatory diseases.