Mirrored dynamics of a wild mosquito population suppression model with Ricker-type survival probability and time delay.

Here, we formulated a delayed mosquito population suppression model including two switching sub-equations, in which we assumed that the growth of the wild mosquito population obeys the Ricker-type density-dependent survival function and the release period of sterile males equals the maturation period of wild mosquitoes. For the time-switched delay model, to tackle with the difficulties brought by the non-monotonicity of its growth term to its dynamical analysis, we employed an essential transformation, derived an auxiliary function and obtained some expected analytical results. Finally, we proved that under certain conditions, the number of periodic solutions and their global attractivities for the delay model mirror that of the corresponding delay-free model. The findings can boost a better understanding of the impact of the time delay on the creation/suppression of oscillations harbored by the mosquito population dynamics and enhance the success of real-world mosquito control programs.

A stochastic dynamical model for nosocomial infections with co-circulation of sensitive and resistant bacterial strains.

Nosocomial infections (hospital-acquired) has been an important public health problem, which may make those patients with infections or involved visitors and hospital personnel at higher risk of worse clinical outcomes or infection, and then consume more healthcare resources. Taking into account the stochasticity of the death and discharge rate of patients staying in hospitals, in this paper, we propose a stochastic dynamical model describing the transmission of nosocomial pathogens among patients admitted for hospital stays. The stochastic terms of the model are incorporated to capture the randomness arising from death and discharge processes of patients. Firstly, a sufficient condition is established for the stochastic extinction of disease. It shows that introducing randomness in the model will result in lower potential of nosocomial outbreaks. Further, we establish a threshold criterion on the existence of stationary distribution and ergodicity for any positive solution of the model. Particularly, the spectral radius form of stochastic threshold value is calculated in the special case. Moreover, the numerical simulations are conducted to both validate the theoretical results and investigate the effect of prevention and control strategies on the prevalence of nosocomial infection. We show that enhancing hygiene, targeting colonized and infected patients, improving antibiotic treatment accuracy, shortening treatment periods are all crucial factors to contain nosocomial infections.

Clinical analysis of secondary glaucoma in Central China.

To describe the epidemiology, clinical and social characteristics, management, and outcomes of patients with secondary glaucoma in Central China, a total of 1,129 cases (1,158 eyes) among 710 males (62.89%) and 419 females (37.11%) were analyzed. The mean age was 53.75 ± 17.11 years. The New Rural Cooperative Medical System (NCMS) played the most important role in reimbursement (60.32%) for secondary glaucoma-related medical expenses. The predominant occupation was "farmer" (53.41%). Neovascularization and trauma were the leading causes of secondary glaucoma. Cases of trauma-induced glaucoma decreased substantially during the coronavirus disease 2019 (COVID-19) pandemic. An education level of senior high school or above was uncommon. Ahmed glaucoma valve implantation was the most commonly performed surgery. At the final follow-up, the overall intraocular pressure (IOP) in patients with vascular disease- and trauma-related secondary glaucoma was 19.53 ± 10.20 mmHg, 20.26 ± 11.75 mmHg, and 16.90 ± 6.72 mmHg, while the mean visual acuity (VA) was 0.33 ± 0.32, 0.34 ± 0.36, and 0.43 ± 0.36. In 814 (70.29%) eyes, the VA was < 0.01. Effective preventive measures for at-risk populations, increased NCMS coverage and the promotion of higher education are necessary. These findings will help ophthalmologists detect secondary glaucoma early and manage it in a timely manner.

Longitudinal Profiling of Plasma Cytokines and Its Association With Postoperative Delirium in Elderly Patients Undergoing Major Lower Limb Surgery: A Prospective Observational Study.

BACKGROUND: Surgery is accompanied by a systemic inflammatory response that may presage delirium in susceptible individuals. Little is known about the trajectory of plasma proinflammatory cytokines and their potential associations with postoperative delirium (POD). The current study longitudinally assessed both pro and anti-inflammatory plasma cytokine response and development of POD in older surgical patients to investigate associations with individual and/or clusters of cytokines that may indicate pathogenic mechanisms. METHODS: A prospective longitudinal study sought to enroll patients >60 years old who were scheduled for major lower limb surgery under general anesthesia. Blood was obtained preoperatively and postoperatively from day 1 through postoperative day 4 for measurement of plasma interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, soluble IL-6 receptor (sIL-6R), IL-10, and tumor necrosis factor-α (TNF-α). Participants were assessed for POD twice daily for 4 days using the confusion assessment method. Trajectory of postoperative changes in plasma cytokines was determined by a group-based trajectory modeling analysis that was informed by distinct cytokines identified by time-dependent Cox regression model. RESULTS: One hundred eighty-eight patients were assessed for eligibility of whom 129 underwent major surgery and 126 had complete datasets for final analysis. POD was diagnosed in 31 of 126 patients (24.6%). Time-dependent Cox regression model identified that higher IL-6 and sIL-6R levels were associated with higher risk of developing POD. A two-cluster model (stable lower and fluctuating higher levels) was considered to be the most statistically appropriate model for IL-6 and sIL-6R trajectory. More participants with fluctuating higher IL-6 were delirious (73.3% vs 18.0%, P = .001) as were those with fluctuating higher sIL-6R (81.3% vs 16.4%, P = .001). CONCLUSIONS: As higher IL-6 and sIL-6R levels were significantly associated with higher risk of POD and the combination is required for IL-6 trans-signaling, it is possible that activation of this pathway may be associated with POD. Furthermore, it will be important to determine whether high levels of the combination of IL-6 and sIL-6R can be an early biomarker for the subsequent development of POD.

Evaluation of effects of 3% diquafosol ophthalmic solution on preocular tear film stability after trabeculectomy.

OBJECTIVES: To determine the potential effects of 3% diquafosol (DQS) on tear film stability after glaucoma surgery. METHODS: We retrospectively reviewed consecutive patients who underwent glaucoma surgery at the glaucoma division of the Henan Eye Institute from January 2020 to January 2021. Clinical parameters, including age, sex, intraocular pressure, and number of glaucoma medications, were tested. Tear film parameters, such as tear meniscus height (TMH), first and average noninvasive tear break-up time (FBUT and ABUT, respectively), and tear film lipid layer grade (TFLL), were evaluated using the Oculus Keratograph 5M. We investigated the differences in clinical and tear film parameters pre- and postoperatively. We compared the baseline and different time points after surgery between the DQS and HA groups and identified the factors associated with changes in the tear film at 8 weeks postoperatively. RESULTS: A total of 101 eyes were included. Early administration of DQS increased TMH, FBUT, ABUT, and TFLL after trabeculectomy (all p < 0.05). In addition, the DQS group showed significantly higher ABUT than the HA group (p < 0.05). DQS use served as an associated parameter for better TMH, FBUT, ABUT, and the TFLL (p < 0.05). DQS and preoperative FBUT were significant independent parameters of postoperative FBUT (p < 0.05). CONCLUSIONS: The present study showed that postoperative TMH, FBUT, ABUT, and TFLL significantly increased after early application of DQS, and the efficacy of ABUT was better than that of HA at the early stage in 8 weeks after trabeculectomy (p < 0.05).

Correlations among Corneal Biomechanical Parameters, Stiffness, and Thickness Measured Using Corvis ST and Pentacam in Patients with Ocular Hypertension.

Background: To preliminary explore the correlations among corneal biomechanical parameters, stiffness, and thickness in patients with ocular hypertension (OHT) before and after treatment with topical antiglaucoma medications. Methods: This was a retrospective study that included 35 eyes with newly diagnosed OHT. Axial length (AL), apical corneal thickness, and minimum corneal thickness were measured using Pentacam. The lengths, velocities, and times of the first and second corneal applanations (A1L, A1V, A1T, A2L, A2V, and A2T, respectively); the highest concavity radius; highest concavity peak distance (PDHC); highest concavity deformation amplitude (DAHC); highest concavity time (HCT); pachymetry (PACH); stress-strain index (SSI); stiffness parameter-A1 (SP-A1); deformation amplitude ratio (DA ratio); integrated radius (IR); Ambrosio's relational thickness horizontal (ARTh); corneal biomechanical index; noncorrected intraocular pressure (IOPnct); and biomechanically corrected IOP (bIOP) values were measured using the corneal visualization Scheimpflug technology (Corvis ST/CST). Results: After 5 weeks of treatment, Goldman applanation tonometer-IOP, IOPnct, bIOP, PACH, A1T, A2V, SSI, SP-A1, and ARTh decreased, but A1V, A2T, PDHC, DAHC, DA ratio, and IR increased significantly (all p < 0.05). SP-A1 and A1T were positively associated with premedication IOP and IOP changes, whereas A1V, A2T, PDHC, and IR were negatively associated (all p < 0.05). DAHC and DA ratio had significantly negative correlations with IOP variations. PDHC was found to be positively correlated with AL (p < 0.05). A positive relationship was noted between SP-A1 and HCT before medication (p < 0.05). Conclusions: SP-A1 was significantly and consistently associated with IOP. HCT might be correlated with SP-A1. SP-A1 and CST parameters could serve as potential biomarkers for evaluating OHT treatment efficacy.

Interleukin-6 trans-signalling in hippocampal CA1 neurones mediates perioperative neurocognitive disorders in mice.

BACKGROUND: Interleukin-6 (IL-6), a pleiotropic cytokine with both degenerative and regenerative properties, is necessary and sufficient to provoke perioperative neurocognitive disorders after aseptic trauma in mice. IL-6 initiates its actions after binding to either membrane-bound IL-6 receptor α (mIL-6Rα) through classical signalling, or soluble IL-6 receptor (IL-6R) through trans-signalling; both signalling pathways require the transducer gp130. We investigated the site and type of IL-6 signalling that pertains in a tibial fracture aseptic trauma model of perioperative neurocognitive disorder. METHODS: Wild-type or genetically altered adult mice that lacked molecules unique to either classical or trans-IL-6 signalling underwent tibial fracture under isoflurane anaesthesia. In separate cohorts, we assessed postoperative memory using a trace fear conditioning paradigm (72 h postoperatively), and post-receptor IL-6 signalling (24 h postoperatively) using phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in CA1 hippocampal neurones. Fracture healing was assessed at postoperative day 15 after inhibiting either both forms of IL-6 signalling with BE0047 or only trans-signalling with sgp130Fc. RESULTS: The surgical phenotype of memory decline (decrease in freezing in trace fear conditioning) and upregulated IL-6 signalling (pSTAT3) did not occur after pretreatment before surgery with either BE0047 or sgp130Fc, or after depleting gp130 from CA1 neurones. The surgical phenotype still occurred when IL-6Rα was depleted in either CA1 hippocampal neurones (freezing time, 38.9% [11.5%] vs 58.4% [12.3%]; pSTAT+ CA1 neurones, 31.7 [4.9] vs 7.0 [3.1]) or microglia (freezing time, 40.1% [13.9%] vs 65.2% [12.6%]; pSTAT+ CA1 neurones, 30.1 [5.5] vs 7.9 [3.2]). In global IL-6Rα-/- mice, hyper-IL-6, the trans-signalling agonist, produced the surgical phenotype when administered i.c.v. (freezing time, 42.4% [8.8%] vs 59.7% [10.4%]; pSTAT+ cells, 29.3 [4.3] vs 10.0 [4.4]). Bone-fracture healing (% of fracture callus comprised of new collagen) was significantly greater with sgp130Fc than with BE0047 (52.2% [8.3%] vs 39.7% [7.9%]). CONCLUSIONS: After orthopaedic trauma, IL-6 produces perioperative neurocognitive disorders through IL-6 trans-signalling in mouse CA1 neurones. Druggable targets of the trans-signalling pathway should be sought to reduce perioperative neurocognitive disorders while allowing the healing properties of classical IL-6 signalling.

Activation of CCL21-GPR174/CCR7 on cardiac fibroblasts underlies myocardial ischemia/reperfusion injury.

Background: The mechanisms underlying myocardial ischemia/reperfusion (I/R) injury are not fully understood. This study aims to explore key candidate genes and potential therapeutic targets for treatment of myocardial I/R injury. Methods: The transcriptional profiles of ventricular myocardium during cardiac arrest, ischemia, and reperfusion were obtained from the Gene Expression Omnibus database. Based on the transcriptional data of GSE6381, functional pathway and process enrichment analyses, protein-protein interaction network, and gene set enrichment analyses were conducted. In the animal experiments, we established the myocardial I/R injury model in mice. We validated the mRNA and protein expression of the key genes using the qPCR and western blots. We further assessed the expression and localization of CCL21 and its receptors using immunofluorescence staining experiments. Results: The microarray analyses identified five key genes (CCL21, XCR1, CXCL13, EDN1, and CASR). Myocardial I/R process in mice resulted in significant myocardial infraction, histological damage, and myocardial apoptosis. The results of qPCR and western blots showed that the expression of CCL21 and CXCL13 were increased following myocardial I/R injury in mice. Furthermore, the immunofluorescence staining results revealed that the expression of GPR174/CCR7 (CCL21 receptors), but not CXCR5 (CXCL13 receptor), was elevated following myocardial I/R injury. Moreover, the activated CCL21-GPR174/CCR7 signaling was located on the cardiac fibroblasts of the myocardium with I/R injury. Conclusion: This study revealed several key factors underlying myocardial I/R injury. Of these, the activation of CCL21-GPR174/CCR7 signaling on cardiac fibroblasts was highlighted, which provides potential therapeutic targets for cardioprotection.

Opioid-free total intravenous anesthesia for thyroid and parathyroid surgery: Protocol for a randomized, double-blind, controlled trial.

Background: Opioid-free anesthesia (OFA) may improve postoperative outcomes by reducing opioid-related adverse effects. This study aims to evaluate the effects of OFA on postoperative nausea and vomiting (PONV), postoperative pain, and 30-day outcomes after thyroid and parathyroid surgery. Methods: This two-center, randomized, double-blind, controlled trial will include 400 adult patients scheduled for thyroid and parathyroid surgery. Patients will be randomly assigned, 1:1 and stratified by sex and site, to an OFA group (esketamine, lidocaine, and dexmedetomidine) or a control group (opioid-based anesthesia with sufentanil). All patients will receive propofol-based total intravenous anesthesia and PONV prophylaxis with dexamethasone and ondansetron. The primary outcome is the incidence of PONV (defined as experiencing any event of nausea, retching, or vomiting) during the first 48 h postoperatively. The secondary outcomes include the severity of PONV, antiemetic rescue therapy, pain scores at rest and while coughing, need for rescue analgesia, perioperative adverse effects related to anesthetics or analgesics (hypotension, bradycardia, hypertension, tachycardia, desaturation, dizziness, headache, hallucination, and nightmare), time to extubation, length of post-anesthesia care unit stay, length of postoperative hospital stay, patient satisfaction, and a composite of 30-day major adverse events (myocardial infarction, cardiac arrest, cerebrovascular accident, coma, acute renal failure, pulmonary embolism, sepsis, septic shock, deep neck space infection, reintubation, reoperation, blood transfusion, failure to wean off ventilator, and death). Analyses will be performed in the modified intention-to-treat population. Discussion: We hypothesize that our OFA regimen reduces PONV after thyroid and parathyroid surgery. We will also investigate whether OFA leads to improvements in postoperative pain and major adverse events. Our results will offer evidence for optimizing anesthesia regimens in patients who undergo thyroid and parathyroid surgical procedures. Clinical trial registration: http://www.chictr.org.cn, identifier: ChiCTR2200059656.

Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a Donation-After-Cardiac-Death Kidney Transplant: A Randomized Clinical Trial.

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 µg/kg/h intraoperatively and 0.1 µg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Exosomal Dvl3 promoted the aggressive phenotypic transformation of RA-FLS via wnt pathway.

OBJECTIVE: This study was performed to explore the function and mechanism of Dvl3 in RA-FLS by exosome intervention. METHODS: The expression pattern of Dvl3 was examined by IHC, WB, and qPCR. Modified exosomes obtained from culturing supernatant of RA-FLS infected with Dvl3 over expression (OE) lentivirus were administrated to the target RA-FLS. The ability of survival, migration, and the production of inflammatory factor influenced by exosomal Dvl3 were detected by CKK8 kits, Tunel, migration test, qPCR, and enzyme-linked immunosorbent assay (ELISA) respectively; Flow cytometry analysis was conducted to explorer the inflammatory moderate role of exosomes on CD4+ T cells. The possible downstream pathways of Dvl3 were screened by qPCR and WB and verified by double luciferase reporter experiment. RESULTS: The expression level of Dvl3 was significantly increased in RA and CIA. Exosomes from the OE group could significantly promote cell proliferation activity, migration/invasion ability. The augment of TNF-α, IL-1ß, IL-17, and IL-21 was observed in exosomal Dvl3-OE group. Th1 and Th17 cells polarisation and cytokines related were both enhanced by Exosomal Dvl3. Over expression of Dvl3 was accompanied by the significant increase of ß-catenin and RhoA activities. CONCLUSION: This study discovered the high expression of Dvl3 of exosomes derived from RA patients which may possessed the ability to promote phenotypic transformation of RA-FLS through Wnt pathway.

Clinical Analysis of Pediatric Glaucoma in Central China.

Purpose: We aimed to describe the characteristics, epidemiology, management, and outcomes of glaucoma in pediatric patients in central China. Methods: This study retrospectively analyzed inpatients with pediatric glaucoma at Henan Provincial People's Hospital, Henan Eye Institute, and Henan Eye Hospital between 2017 and 2020. Results: Overall, 239 cases (276 eyes) of pediatric glaucoma in patients, comprising 87 girls (36.40%) and 152 boys (63.60%) were analyzed. The mean age was 6.65 ± 4.46, and 2.93% of the patients had a family history of glaucoma. Primary congenital glaucoma (PCG) was the most common type of glaucoma, followed by traumatic glaucoma in 8.33% of the patients, which was considered secondary glaucoma. The most common signs and symptoms were elevated intraocular pressure (IOP) and eye pain. Trabeculotomy (Trab) and microcatheter-assisted 360° trabeculotomy (MAT) combined with Trab were the most commonly performed surgeries. The IOP of patients with PCG, juvenile open-angle glaucoma (JOAG), and secondary glaucoma were 15.27 ± 7.48 mmHg, 17.16 ± 10.05, and 18.65 ± 8.55, respectively, at the final follow up. The rate of re-operations in patients with PCG, JOAG, and secondary glaucoma were 9.15%, 6.78%, and 4.69%, respectively. The mean visual acuity of the eyes with PCG, JOAG, and secondary glaucoma was 0.79 ± 0.68, 0.51 ± 0.48, and 0.53 ± 0.50, respectively. Conclusion: PCG, JOAG, and traumatic glaucoma were the most prevalent subtypes in patients with pediatric glaucoma in central China. Trab and MAT combined with Trab were the most common interventions used in this study. Pediatric amblyopia might require full attention during the entire treatment, especially after glaucoma surgery. Effective preventive measures and more public education on glaucoma prevention and the importance of early diagnosis and treatment is necessary.

Dynamical Behavior of SEIR-SVS Epidemic Models with Nonlinear Incidence and Vaccination.

For some infectious diseases such as mumps, HBV, there is evidence showing that vaccinated individuals always lose their immunity at different rates depending on the inoculation time. In this paper, we propose an age-structured epidemic model using a step function to describe the rate at which vaccinated individuals lose immunity and reduce the age-structured epidemic model to the delay differential model. For the age-structured model, we consider the positivity, boundedness, and compactness of the semiflow and study global stability of equilibria by constructing appropriate Lyapunov functionals. Moreover, for the reduced delay differential equation model, we study the existence of the endemic equilibrium and prove the global stability of equilibria. Finally, some numerical simulations are provided to support our theoretical results and a brief discussion is given.

Esketamine as an Adjuvant to Ciprofol or Propofol Sedation for Same-Day Bidirectional Endoscopy: Protocol for a Randomized, Double-Blind, Controlled Trial With Factorial Design.

Background: Same-day esophagogastroduodenoscopy and colonoscopy procedures under sedation have been increasingly performed. This study aims to assess the effects of esketamine combined with ciprofol (a novel anesthetic/sedative agent) or propofol on respiratory and hemodynamic adverse events in patients undergoing same-day bidirectional endoscopy. Methods: This is a prospective, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. A total of 180 adult patients scheduled for same-day bidirectional endoscopy under sedation will be randomized, in a 1:1:1:1 ratio, to receive 1 of 4 sedation regimens: 1) ciprofol and esketamine, 2) propofol and esketamine, 3) ciprofol and normal saline placebo, or 4) propofol and normal saline placebo. The primary outcome is a composite of desaturation [peripheral oxygen saturation (SpO2) < 95%] and hypotension [mean blood pressure (MBP) < 65 mmHg or decrease in MBP ≥20% of baseline] during the sedation and in the recovery room. Secondary outcomes include episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), bradycardia, postoperative nausea and vomiting, dizziness or headache, hallucination or nightmare, injection pain, pain scores and fatigue scores, endoscopist satisfaction, and patient satisfaction. Data will be analyzed on the modified intention-to-treat basis. Discussion: We hypothesize that esketamine as an adjuvant to ciprofol or propofol sedation would improve cardiorespiratory stability. In addition, the potential interactions between interventions will be explored using the factorial design. The results of this trial will provide evidence for daily practice of sedation regimens for same-day bidirectional endoscopy. Clinical Trial Registration: Chinese Clinical Trials Registry, Identifier ChiCTR2100052523.

Antibiotic Stewardship Strategies and Their Association With Antibiotic Overuse After Hospital Discharge: An Analysis of the Reducing Overuse of Antibiotics at Discharge (Road) Home Framework.

BACKGROUND: Strategies to optimize antibiotic prescribing at discharge are not well understood. METHODS: In fall 2019, we surveyed 39 Michigan hospitals on their antibiotic stewardship strategies. The association of reported strategies with discharge antibiotic overuse (unnecessary, excess, suboptimal fluoroquinolones) for community-acquired pneumonia (CAP) and urinary tract infection (UTI) was evaluated in 2 ways: (1) all strategies assumed equal weight and (2) strategies were weighted based on the ROAD (Reducing Overuse of Antibiotics at Discharge) Home Framework (ie, Tier 1-Critical infrastructure, Tier 2-Broad inpatient interventions, Tier 3-Discharge-specific strategies) with Tier 3 strategies receiving the highest weight. RESULTS: Between 1 July 2017 and 30 July 2019, 39 hospitals with 20 444 patients (56.5% CAP; 43.5% UTI) were included. Survey response was 100%. Hospitals reported a median (interquartile range [IQR]) 12 (9-14) of 34 possible stewardship strategies. On analyses of individual stewardship strategies, the Tier 3 intervention, review of antibiotics prior to discharge, was the only strategy consistently associated with lower antibiotic overuse at discharge (adjusted incident rate ratio [aIRR] 0.543, 95% confidence interval [CI]: .335-.878). On multivariable analysis, weighting by ROAD Home tier predicted antibiotic overuse at discharge for both CAP and UTI. For diseases combined, having more weighted strategies was associated with lower antibiotic overuse at discharge (aIRR 0.957, 95% CI: .927-.987, per weighted intervention); discharge-specific stewardship strategies were associated with a 12.4% relative decrease in antibiotic overuse days at discharge. CONCLUSIONS: The more stewardship strategies a hospital reported, the lower its antibiotic overuse at discharge. However, Tier 3, or discharge-specific strategies, appeared to have the largest effect on antibiotic prescribing at discharge.

Existence and stability of two periodic solutions for an interactive wild and sterile mosquitoes model.

In this paper, we study the periodic and stable dynamics of an interactive wild and sterile mosquito population model with density-dependent survival probability. We find a release amount upper bound G∗, depending on the release waiting period T, such that the model has exactly two periodic solutions, with one stable and another unstable, provided that the release amount does not exceed G∗. A numerical example is also given to illustrate our results.

Effects of anesthetic depth on postoperative pain and delirium: a meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: Whether anesthetic depth affects postoperative outcomes remains controversial. This meta-analysis aimed to evaluate the effects of deep vs. light anesthesia on postoperative pain, cognitive function, recovery from anesthesia, complications, and mortality. METHODS: PubMed, EMBASE, and Cochrane CENTRAL databases were searched until January 2022 for randomized controlled trials comparing deep and light anesthesia in adult surgical patients. The co-primary outcomes were postoperative pain and delirium (assessed using the confusion assessment method). We conducted a meta-analysis using a random-effects model. We assessed publication bias using the Begg's rank correlation test and Egger's linear regression. We evaluated the evidence using the trial sequential analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We conducted subgroup analyses for pain scores at different postoperative time points and delirium according to cardiac or non-cardiac surgery. RESULTS: A total of 26 trials with 10,743 patients were included. Deep anesthesia compared with light anesthesia (a mean difference in bispectral index of -12 to -11) was associated with lower pain scores at rest at 0 to 1 h postoperatively (weighted mean difference = -0.72, 95% confidence interval [CI] = -1.25 to -0.18, P  = 0.009; moderate-quality evidence) and an increased incidence of postoperative delirium (24.95% vs. 15.92%; risk ratio = 1.57, 95% CI = 1.28-1.91, P  < 0.0001; high-quality evidence). No publication bias was detected. For the exploratory secondary outcomes, deep anesthesia was associated with prolonged postoperative recovery, without affecting neurocognitive outcomes, major complications, or mortality. In the subgroup analyses, the deep anesthesia group had lower pain scores at rest and on movement during 24 h postoperatively, without statistically significant subgroup differences, and deep anesthesia was associated with an increased incidence of delirium after non-cardiac and cardiac surgeries, without statistically significant subgroup differences. CONCLUSIONS: Deep anesthesia reduced early postoperative pain but increased postoperative delirium. The current evidence does not support the use of deep anesthesia in clinical practice.

Remote Ischemic Preconditioning Reduces Acute Kidney Injury After Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery. METHODS: PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis. RESULTS: A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis. CONCLUSIONS: This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.

Deep Neuromuscular Blockade Combined with Low Pneumoperitoneum Pressure for Nociceptive Recovery After Major Laparoscopic Gastrointestinal Surgery: Study Protocol for a Randomized Controlled Trial.

PURPOSE: Patients undergoing major laparoscopic surgery often experience significant pain and postoperative nausea and vomiting (PONV). Deep neuromuscular block (NMB) improves surgical conditions and facilitates the application of low intra-abdominal pressure (IAP), which may be beneficial for these patients. This study is designed to determine the effects of deep NMB combined with low IAP, as compared to moderate NMB combined with standard IAP, on patients' nociceptive recovery after major laparoscopic gastrointestinal surgery. STUDY DESIGN AND METHODS: This single-center randomized controlled trial will include 220 patients scheduled for major laparoscopic gastrointestinal surgery (lasts for ≥ 90 minutes). Patients will be randomly assigned, with a 1:1 ratio, into a deep NMB + low IAP group (train of four = 0, post-tetanic count = 1-3, IAP = 8 mmHg) and a moderate NMB + standard IAP group (train of four = 1-3, IAP = 12 mmHg). If the surgical workspace is inadequate, the surgeons can request a step increase of 1 mmHg in IAP during 3-min intervals. The upper limit of IAP will be set at 15 mmHg. Postoperative recovery will be assessed using the postoperative quality recovery scale (PQRS). The primary outcome of this trial is the PQRS nociceptive recovery (including pain and PONV) at postoperative day (POD) 1. The secondary outcomes include recovery in other PQRS domains at POD 1, and recovery in all PQRS domains in a post-anesthesia care unit, at POD 3 in the surgical wards, at hospital discharge, and at postoperative 30 days. For the sample size estimation, 110 patients in each group (220 in total) would be needed to detect an absolute increase rate of 20% in the PQRS nociceptive domain in the deep NMB + low IAP group at POD 1. DISCUSSION: This study investigates the effects of deep NMB combined with low IAP on postoperative PQRS nociceptive recovery in patients undergoing major laparoscopic gastrointestinal surgery. We expect that this deep NMB + low IAP strategy would improve postoperative pain and PONV following major laparoscopic gastrointestinal surgery.

Effect of Intraoperative Dexmedetomidine on Recovery of Gastrointestinal Function After Abdominal Surgery in Older Adults: A Randomized Clinical Trial.

Importance: Postoperative ileus is common after abdominal surgery, and small clinical studies have reported that intraoperative administration of dexmedetomidine may be associated with improvements in postoperative gastrointestinal function. However, findings have been inconsistent and study samples have been small. Further examination of the effects of intraoperative dexmedetomidine on postoperative gastrointestinal function is needed. Objective: To evaluate the effects of intraoperative intravenous dexmedetomidine vs placebo on postoperative gastrointestinal function among older patients undergoing abdominal surgery. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at the First Affiliated Hospital of Anhui Medical University in Hefei, China (lead site), and 12 other tertiary hospitals in Anhui Province, China. A total of 808 participants aged 60 years or older who were scheduled to receive abdominal surgery with an expected surgical duration of 1 to 6 hours were enrolled. The study was conducted from August 21, 2018, to December 9, 2019. Interventions: Dexmedetomidine infusion (a loading dose of 0.5 µg/kg over 15 minutes followed by a maintenance dose of 0.2 µg/kg per hour) or placebo infusion (normal saline) during surgery. Main Outcomes and Measures: The primary outcome was time to first flatus. Secondary outcomes were postoperative gastrointestinal function measured by the I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) scoring system, time to first feces, time to first oral feeding, incidence of delirium, pain scores, sleep quality, postoperative nausea and vomiting, hospital costs, and hospital length of stay. Results: Among 808 patients enrolled, 404 were randomized to receive intraoperative dexmedetomidine, and 404 were randomized to receive placebo. In total, 133 patients (60 in the dexmedetomidine group and 73 in the placebo group) were excluded because of protocol deviations, and 675 patients (344 in the dexmedetomidine group and 331 in the placebo group; mean [SD] age, 70.2 [6.1] years; 445 men [65.9%]) were included in the per-protocol analysis. The dexmedetomidine group had a significantly shorter time to first flatus (median, 65 hours [IQR, 48-78 hours] vs 78 hours [62-93 hours], respectively; P < .001), time to first feces (median, 85 hours [IQR, 68-115 hours] vs 98 hours [IQR, 74-121 hours]; P = .001), and hospital length of stay (median, 13 days [IQR, 10-17 days] vs 15 days [IQR, 11-18 days]; P = .005) than the control group. Postoperative gastrointestinal function (as measured by the I-FEED score) and delirium incidence were similar in the dexmedetomidine and control groups (eg, 248 patients [72.1%] vs 254 patients [76.7%], respectively, had I-FEED scores indicating normal postoperative gastrointestinal function; 18 patients [5.2%] vs 12 patients [3.6%] had delirium on postoperative day 3). Conclusions and Relevance: In this randomized clinical trial, the administration of intraoperative dexmedetomidine reduced the time to first flatus, time to first feces, and length of stay after abdominal surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative recovery of gastrointestinal function among older adults. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800017232.