Nirmatrelvir and ritonavir combination against COVID-19 caused by omicron BA.2.2 in the elderly: A single-center large observational study.

BACKGROUND: Since coronavirus 2019 (COVID-19) swept the world, a variety of novel therapeutic and prevention strategies have been developed, among which nirmatrelvir-ritonavir is highly recommended. We intended to assess the effectiveness and safety of nirmatrelvir-ritonavir in the elderly mild-to-moderate COVID-19 population caused by the omicron BA.2.2 variant in real-world settings. METHODS: An observational study was conducted retrospectively to review the outcomes of mild-to-moderate COVID-19 patients admitted between April 26 and June 30, 2022. Patients' baseline characteristics were collected and assessed. Participants in the intervention group were administered nirmatrelvir-ritonavir in addition to standard care, whereas those in the control group only received standard care. The primary outcome was the duration between the initial positive reverse-transcription polymerase chain reaction (RT-PCR) test and the subsequent conversion to a negative result. RESULTS: The analysis included 324 patients who were administered nirmatrelvir-ritonavir and an equal number of control patients. The patient characteristics in both groups were evenly matched. The average duration from the initial positive RT-PCR to negative conversion was similar in both groups (16.2 ± 5.0 vs. 16.1 ± 6.3 days, p = .83). Control patients exhibited slower conversion in comparison to patients who received nirmatrelvir-ritonavir treatment within 10 days of symptom onset. CONCLUSIONS: These findings suggest that administering nirmatrelvir-ritonavir within 10 days of symptom onset could potentially reduce the time it takes for SARS-CoV-2-infected patients to negative RT-PCR results, thereby expanding the current usage guidelines for nirmatrelvir-ritonavir.

Prediction of risk factors of sleep disturbance in patients undergoing total hip arthroplasty.

The purpose of this study was to assess sleep quality in patients undergoing total hip arthroplasty (THA) from preoperatively to 12 weeks postoperatively and to establish a risk predictor for postoperative sleep disturbance to enable early care and intervention. A self-designed data collection form was used. Patients were assessed preoperatively and at 5 postoperative time points using visual analog scale (VAS) for pain, sleep quality and neuropsychological status with the following assessment tools: the Chinese versions of the Pittsburgh Sleep Quality Index (CPSQI), the Epworth Sleepiness Scale (CESS), the Zung Self-Rating Anxiety Scale (ZSAS) and the Epidemiological Studies Depression Scale (CESD). Univariate and multivariate logistic regression analysis was used for the identification of risk factors for postoperative sleep disturbance. The receiver operating characteristic (ROC) curve was plotted to evaluate the regression model. Of the 290 eligible patients, 193 (133 women) were included in the study. There was a 60.6% prevalence of preoperative sleep disturbance. The CPSQI score increased significantly at 2 weeks postoperatively compared to preoperative baseline, but appeared to decrease at 4 weeks postoperatively. Multivariate logistic regression analysis showed that pain (VAS score: OR = 1.202 [95% CI = 1.002-1.446, P < 0.05]), daytime sleepiness (CESS score: OR = 1.134 [95% CI = 1.015-1.267, P < 0.05]) and anxiety (ZSAS score: OR = 1.396 [95% CI = 1.184-1.645, P < 0.001]) were risk factors associated with postoperative sleep disturbance at 2 weeks. The ROC curve showed that the AUC was 0.762, the sensitivity was 83.19% and the specificity was 64.86%. Postoperative sleep disturbance is highly prevalent in the first 2 weeks after THA. The risk prediction model constructed according to the above factors has good discriminant ability for the risk prediction of sleep disturbance after THA. The use of this risk prediction model can improve the recognition of patients and medical providers and has good ability to guide clinical nursing observation and early screening of sleep disturbance after THA.

Influence of Aging on Outcomes of Sacubitril/Valsartan in Hypertensive Patients with Heart Failure: A Multicenter Retrospective Study.

BACKGROUND: The aim of this study was to investigate the influence of aging on the effectiveness and tolerance of sacubitril/valsartan (sac/val) among hypertensive patients complicated with heart failure in a real-world setting. METHODS: This multicenter, retrospective study included patients (≥18 years old) admitted with a diagnosis of hypertension and heart failure, starting sac/val therapy between January 2020 and December 2021 from 3 medical centers. Patients were grouped by the cutoff age of 65 years. Outcomes were collected 31-365 days after the initiation of sac/val and were compared in a matched cohort after 1: 1 propensity score matching (PSM). RESULTS: A total of 794 patients were finally analyzed. Blood pressure and cardiac functions improved significantly compared with values at baseline. There were 269 patients in each cohort (<65 years and ≥65 years) after PSM. After PSM, the incidence of hyperuricemia and hypotension in the elderly patients (≥65 years) was significantly higher than in those <65 years of age. Kaplan-Meier estimate suggested that the cumulative incidence of new or recurrent cardiovascular events increased significantly at the age of ≥65 years after the point of 3 months (log-rank P =.00087). CONCLUSION: Sac/val benefited patients in both cohorts by improving blood pressure and cardiac function. Elderly patients (≥65 years) were susceptible to hypotension, low diastolic blood pressure, hyperuricemia, and underwent cardiac-related readmissions more frequently.

Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure.

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n = 82; dabigatran, n = 38). Blood samples were obtained from left atrium (LA) and left atrial appendage (LAA) during the operation and fasting blood samples on the same day of LAAC and 45 days after discharge. The biochemical indicators, thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), von Willebrand factor (vWF), and CD40 ligand (CD40L), were measured by enzyme-linked immunosorbent assay. The primary endpoints of this study were the efficacy and safety characteristics of different antithrombotic strategies, including DRT incidence, stroke or transient ischemic attack, systemic embolism, and clinical major and nonmajor bleeding complications during the follow-up of 180 days. The results revealed that TAT, vWF, sP-selectin, and CD40L levels in vein were significantly reduced by 2.4% (p = 0.043), 5.0% (p < 0.001), 8.7% (p < 0.001), and 2.5% (p = 0.043) from their baseline levels after rivaroxaban treatment. Conversely, no significant changes were detected in the dabigatran group. Furthermore, the plasma levels of platelet activation biomarkers (CD40L and sP-selectin) in both LA and LAA groups were significantly lower after anticoagulation with rivaroxaban, as compared to dabigatran treatment (CD40L: 554.62 ± 155.54 vs. 445.02 ± 130.04 for LA p = 0.0013, 578.51 ± 156.28 vs. 480.13 ± 164.37 for LAA p = 0.0052; sP-selectin: 2849.07 ± 846.69 vs. 2225.54 ± 799.96 for LA p = 0.0105, 2915.52 ± 1402.40 vs. 2203.41 ± 1061.67 for LAA p = 0.0022). Notably, the present study suggests that rivaroxaban may be more effective in the prevention of DRT for patients undergoing LAAC.

Clinical efficacy of clopidogrel and ticagrelor in patients undergoing off-pump coronary artery bypass grafting: a retrospective cohort study.

BACKGROUND: Ticagrelor is reportedly more effective than clopidogrel in preventing atherothrombotic events in patients with percutaneous coronary intervention. However, the optimal antiplatelet therapy strategy after off-pump coronary artery bypass grafting (OPCABG) is yet to be established. MATERIALS AND METHODS: This study was performed using the prospectively-maintained database at our institution. Patients who underwent OPCABG were divided into the clopidogrel and the ticagrelor groups. Propensity score matching analysis was performed between the two groups. The clinical outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of vascular death, myocardial infarction, or stroke 1 year after surgery. RESULTS: In total, 545 patients completed the entire follow-up assessment. After propensity score matching, 232 patients each were included in the clopidogrel and ticagrelor groups. The primary outcome occurred in 7.8% and 4.3% of patients in the clopidogrel and ticagrelor groups, respectively (P=0.113). CYP2C19 variants (*2, *3, and *17) did not impact the clinical outcomes, regardless of the use of clopidogrel or ticagrelor. The rates of MACE were significantly lower in patients carrying the ABCB1 C3435T CT/TT genotypes in the ticagrelor group than in those carrying the ABCB1 C3435T CC genotype in the clopidogrel group (1.4% vs. 9.1%, adjusted P=0.030), as well as those carrying the ABCB1 C3435T CC genotype in the ticagrelor group (1.4% vs. 8.9%, adjusted P=0.036). The ABCB1 C3435T CC genotype was significantly associated with the incidence of 1-year MACE (HR=1.558, 95% CI 1.109-2.188, P=0.011). Patients who experienced severe perioperative bleeding exhibited a significantly higher incidence of MACE than those who did not experience severe perioperative bleeding (14.0% vs. 4.9%, adjusted P=0.007). CONCLUSION: There was no significant difference in the 1-year MACE between patients receiving clopidogrel and those receiving ticagrelor after OPCABG. Notably, The ABCB1 C3435T CC genotype was related to a higher risk of MACE.

Principles of Optimal Antithrombotic Therapy for Iliac VEnous Stenting (POATIVES): A national expert-based Delphi consensus study.

OBJECTIVE: Management of antithrombotic therapy in patients undergoing venous stents has not yet reached consensus, and there are not any recommendations from published guidelines. We undertook a Delphi consensus from Chinese experts to develop recommendations regarding the preferred antithrombotic therapy in patients following venous stenting. METHODS: The phase 1 questionnaire was comprised of three clinical scenarios of venous stenting for non-thrombotic iliac vein lesions (NIVL), acute deep vein thrombosis (DVT), and post-thrombotic syndrome (PTS) and was sent to venous practitioners across China. In phase 2, the results of phase 1 were distributed to a panel of experts for evaluation along with a questionnaire encompassing a series of statements produced during phase 1. A modified Delphi method was used to reach consensus on recommendations through two rounds of surveys. RESULTS: The phase 1 questionnaire was completed by 283 respondents. In phase 2, an expert panel consisting of 28 vascular surgeons and interventional radiologists was assembled and voted 17 statements relating to antithrombotic management after venous stenting for NIVL (4 statements), DVT (6 statements), and PTS (7 statements). The majority of the statements about the antithrombotic agent selection received a high consensus strength. CONCLUSIONS: Based on the national Delphi consensus of Chinese experts regarding antithrombotic therapy following iliac venous stenting in three common scenarios, most of the statements could be used to guide antithrombotic management following venous stenting. Further studies are required to clarify controversial issues including the dose and duration of anticoagulants, the role of antiplatelet agents, especially in patients with NIVL.

A Novel Body Mass Index-Based Thromboembolic Risk Score for Overweight Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: A novel risk prediction model appears to be urgently required to improve the assessment of thrombotic risk in overweight patients with nonvalvular atrial fibrillation (NVAF). We developed a novel body mass index (BMI)-based thromboembolic risk score (namely AB2S score) for these patients. METHODS: A total of 952 overweight patients with NVAF were retrospectively enrolled in this study with a 12-month follow-up. The primary endpoint was 1-year systemic thromboembolism and the time to thrombosis (TTT). The candidate risk variables identified by logistic regression analysis were included in the final nomogram model to construct AB2S score. The measures of model fit were evaluated using area under the curve (AUC), C-statistic, and calibration curve. The performance comparison of the AB2S score to the CHADS2 and CHA2DS2-VASc score was performed in terms of the AUC and decision analysis curve (DAC). RESULTS: The AB2S score was constructed using 7 candidate risk variables, including a 3-category BMI (25 to 30, 30 to 34, or ≥35 kg/m2). It yielded a c-index of 0.885 (95% CI, 0.814-0.954) and an AUC of 0.885 (95% CI, 0.815-0.955) for predicting 1-year systemic thromboembolism in patients with NVAF. Compared to the CHADS2 score and CHA2DS2-VASc score, the AB2S score had greater AUC and DAC values in predicting the thromboembolic risk and better risk stratification in TTT (P <.0001, P =.082, respectively). CONCLUSION: Our results highlighted the importance of a BMI-based AB2S score in determining systemic thromboembolism risk in overweight patients with NVAF, which may aid in decision-making for these patients to balance the effectiveness of anticoagulation from the underlying thrombotic risk.

Clinical characteristics and outcomes of patients with primary liver cancer and immune checkpoint inhibitor-associated adrenal insufficiency: A retrospective cohort study.

BACKGROUND: Adrenal insufficiency (AI) is a rare, but potentially serious adverse event associated with immune checkpoint inhibitors (ICIs). This study aims to examine the incidence, clinical features and the clinical correlation between occurrence of AI and efficacy in primary liver cancer (PLC) patients treated with ICIs; and to evaluate the significance of the continuation of ICIs treatment in PLC patients who developed AI. METHODS: Between January 2020 and March 2022, 47 PLC patients with ICIs-associated AI (AI cohort) were screened from Zhongshan Hospital, Fudan university, a general hospital in China. Between December 2019 and August 2021, 419 PLC patients who were treated with ICIs were reviewed to identify those without immune- associated adverse events (irAEs) (control cohort). Clinical features and outcomes of the PLC patients from the two cohorts were compared. RESULTS: Totally, 47 PLC patients with AI (AI cohort) and 63 PLC patients without irAEs (control cohort) were included. The incidence of grades 3-4 of AI and all irAEs were 40.4 % and 48.9 %, respectively. The median three-year survival was significantly longer in the AI cohort than that in the control cohort (26.3 months (95 % CI: 18.9--33.5) vs.16.1 months (95 % CI:10.4--21.7); p = 0.021). Multivariable cox proportional hazards regression model showed that the development of AI remained significantly associated with improved overall survival (HR = 0.561; p = 0.033) in the adjusted regression analysis. CONCLUSION: The current study demonstrated that PLC patients undergoing ICIs therapy and developing AI after ICIs treatment had favorable survival outcomes compared to those without irAEs.

Sacubitril/Valsartan in Heart Failure with Hypertension Patients: Real-World Experiences on Different Ages, Drug Doses, and Renal Functions.

INTRODUCTION: Hypertension is a significant risk factor in heart failure for worldwide patients. More than half of hypertensive patients suffer from heart failure. Recently, sacubitril/valsartan (sac/val) has been approved as an antihypertensive agent in China and Japan. Additionally, it is not approved for treating hypertension in Europe or the USA. AIM: To accumulate more real-world experiences to investigate the effectiveness and optimize clinical medication of sac/val in hypertensive patients with heart failure. METHODS: We retrospectively enrolled adult patients diagnosed with hypertension (HTN) and heart failure (HF) and newly treated with sac/val. The baseline characteristics and clinical outcomes were retrospectively extracted from electronic medical records (EMR) in three centers. The efficacy and safety of sac/val were first analyzed in all enrolled patients. Stratified analyses were conducted in patients with different ages (≥ 65, < 65), maximum tolerated doses (≥ 200 mg/days, < 200 mg/days), and renal functions (e-GFR ≥ 60 ml/min/1.73 m2, < 60 ml/min/1.73 m2). RESULTS: Overall, 794 patients diagnosed with both HF and HTN were included in our study. During follow-up, significant reductions were found in blood pressure (BP) (SBP 12.8 ± 21.2 mmHg, P < 0.001, DBP 7.1 ± 16.5 mmHg, P < 0.001), and cardiac biomarkers (cardiac troponin 1.78 ± 19.1 ng/mL, P < 0.001, NT-proBNP 1403 ± 6937 pg/mL, P < 0.001) from baseline. In stratification analyses, the lower dosage group earned a higher BP control rate (83.4% vs. 75.6%, P = 0.025) and an overall improvement rate of cardiac indicators (61.3% vs. 48.0%, P = 0.002). The younger patients' group had significantly less cumulative hazard of recurrent cerebral-cardiovascular events than the elder group (log-rank P value < 0.001). Patients with renal dysfunction were observed with more AE incidences. CONCLUSIONS: Sac/val could reduce BP and improve cardiac structural and functional parameters in hypertensive patients with HF, even with less than target doses. However, more attention should be paid to older patients and renal dysfunction patients when using sac/val because of additional risks in adverse events.

Combination of Rivaroxaban and Amiodarone Increases Bleeding in Patients With Atrial Fibrillation.

BACKGROUND: Rivaroxaban and amiodarone are commonly used for treating patients with atrial fibrillation. Drug-drug interactions between rivaroxaban and amiodarone may increase exposure to rivaroxaban. However, the clinical relevance of this drug-drug interaction is still not clear. OBJECTIVE: The aim was to investigate the risk of bleeding in patients receiving a combination of rivaroxaban and amiodarone. METHODS: This was a prospective observational study in which we included atrial fibrillation patients treated with rivaroxaban. The patients were divided into the rivaroxaban group and the combination of rivaroxaban and amiodarone group (the combination group). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust between-group differences. The primary endpoint was defined as the time to the first occurrence of a composite of major, clinically relevant nonmajor, and minor bleeding. RESULTS: In total, 481 atrial fibrillation patients were included in the analysis. After PSM, 154 patients in the rivaroxaban group were matched with 154 patients in the combination group. The bleeding events mainly consisted of clinically relevant nonmajor and minor bleeding. Only one patient experienced major bleeding. The primary outcome was recorded in 26.0% of patients in the combination group and 10.4% of patients in the rivaroxaban group (hazard ratio = 2.76, 95% CI = 1.55-4.93, P < 0.001). The bleeding risk was significantly higher in the combination group compared with that in the rivaroxaban group in the IPTW and stabilized IPTW analyses (hazard ratio = 2.17, 95% CI = 1.32-3.56, P = 0.002). CONCLUSION AND RELEVANCE: The combination of rivaroxaban and amiodarone increased the risk of bleeding in patients with atrial fibrillation, especially clinically relevant nonmajor and minor bleeding. Physicians prescribing rivaroxaban and amiodarone together should be concerned about an increase in the risk of nonmajor bleeding.

External evaluation of the predictive performance of published population pharmacokinetic models of linezolid in adult patients.

OBJECTIVES: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. METHODS: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. RESULTS: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance. CONCLUSION: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.

Mutant CYP3A4/5 Correlated with Clinical Outcomes by Affecting Rivaroxaban Pharmacokinetics and Pharmacodynamics in Patients with Atrial Fibrillation.

PURPOSE: This study was designed to investigate the impact of single-nucleotide polymorphism-encoded cytochrome P450 enzymes (CYP3A4/5) on clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) based on pharmacokinetics and pharmacodynamics (PK/PD) aspects. METHOD: A prospective study enrolling 165 rivaroxaban-treated patients with NVAF was conducted. Genotyping of CYP3A4 (rs2242480, rs2246709, rs3735451, and rs4646440) and CYP3A5 (rs776746) was performed to explore their impact on the trough plasma concentrations (Ctrough) of rivaroxaban, coagulation indicators at the Ctrough including activated partial thromboplastin time (APTT) and prothrombin time (PT), and clinical outcomes. RESULTS: Patients with mutant genotype CYP3A4 (rs2242480, rs2246709, and rs3735451) and CYP3A5 (rs776746) had higher levels of rivaroxaban Ctrough, PT values than that of wild-type. Furthermore, a positive relationship was revealed between Ctrough and PT (r = 0.212, p = 0.007), while no significant correlation was found between Ctrough and APTT. Regarding the clinical outcomes, the minor allele carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were associated with higher incidence of minor bleeding (p = 0.028 and p = 0.038, respectively) and were identified as the independent risk factors of minor bleeding treated with rivaroxaban (p = 0.024 and p = 0.036, respectively), with the receiver operating characteristic (ROC) curve validated (AUC = 0.8956, 95% CI: 0.829-0.962). CONCLUSION: The CYP3A4 polymorphisms (rs2242480, rs2246709, and rs3735451) and CYP3A5 rs776746 were associated with variations in rivaroxaban PK/PD. The minor allele (C) carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were correlated with clinical outcomes.

Immune checkpoint inhibitor-associated adrenal insufficiency in Chinese cancer patients: a retrospective analysis.

PURPOSE: Immune checkpoint inhibitors (ICIs) are of great success in cancer therapy. This study aimed to identify adrenal insufficiency (AI) associated with immune checkpoint inhibitor (ICI) treatment in cancer patients receiving steroid replacement therapy and report the clinical characteristics of ICI-associated AI and concurrent immune-associated adverse events (irAEs). METHODS: Patients prescribed cortisone acetate between January 2020 and March 2022 were reviewed to identify AI associated with ICI treatment. Data collected included indication of ICI (cancer type), drug characteristics, and outcomes. RESULTS: A total of 101 patients were diagnosed with AI following treatment with ICIs. The median age was 64 years (range 22-83 years); 73.3% of the patients were male. Median time to develop primary AI and secondary AI after starting ICI therapy was 200.5 (35-280) days and 178 (16-562) days, respectively. Concurrent irAEs occurred in 67 (66.3%) patients and included 63 (62.4%) endocrine irAEs. Log-rank test showed that there was a trend toward higher likelihood of death at 120-day follow-up in patients initially receiving intravenous hydrocortisone compared with those receiving oral cortisone acetate after diagnosis of AI (p = 0.029). CONCLUSION: This retrospective study comprehensively documented the clinical characterization of ICI-associated AI. Those initially receiving intravenous hydrocortisone after diagnosis of AI were associated with higher likelihood of death. Physicians should be aware of the variability of ICI-associated irAEs early in the treatment, early diagnoses, and timely management should be made.

Soluble interleukin-2 receptor combined with interleukin-8 is a powerful predictor of future adverse cardiovascular events in patients with acute myocardial infarction.

Background: Little is known about the role of interleukin (IL) in patients with acute myocardial infarction (MI), especially soluble IL-2 receptor (sIL-2R) and IL-8. We aim to evaluate, in MI patients, the predictive value of serum sIL-2R and IL-8 for future major adverse cardiovascular events (MACEs), and compare them with current biomarkers reflecting myocardial inflammation and injury. Methods: This was a prospective, single-center cohort study. We measured serum concentrations of IL-1ß, sIL-2R, IL-6, IL-8 and IL-10. Levels of current biomarkers for predicting MACEs were measured, including high-sensitivity C reactive protein, cardiac troponin T and N-terminal pro-brain natriuretic peptide. Clinical events were collected during 1-year and a median of 2.2 years (long-term) follow-up. Results: Twenty-four patients (13.8%, 24/173) experienced MACEs during 1-year follow-up and 40 patients (23.1%, 40/173) during long-term follow-up. Of the five interleukins studied, only sIL-2R and IL-8 were independently associated with endpoints during 1-year or long-term follow-up. Patients with high sIL-2R or IL-8 levels (higher than the cutoff value) had a significantly higher risk of MACEs during 1-year (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) and long-term (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) follow-up. Receiver operator characteristic curve analysis regarding predictive accuracy for MACEs during 1-year follow-up showed that the area under the curve for sIL-2R, IL-8, sIL-2R combined with IL-8 was 0.66 (0.54-0.79, p = 0.011), 0.69 (0.56-0.82, p < 0.001) and 0.720 (0.59-0.85, p < 0.001), whose predictive value were superior to that of current biomarkers. The addition of sIL-2R combined with IL-8 to the existing prediction model resulted in a significant improvement in predictive power (p = 0.029), prompting a 20.8% increase in the proportion of correct classifications. Conclusions: High serum sIL-2R combined with IL-8 levels was significantly associated with MACEs during follow-up in patients with MI, suggesting that sIL-2R combined with IL-8 may be a helpful biomarker for identifying the increased risk of new cardiovascular events. IL-2 and IL-8 would be promising therapeutic targets for anti-inflammatory therapy.

Cost-effectiveness of ceftazidime/avibactam plus metronidazole versus meropenem as first-line empiric therapy for the treatment of complicated intra-abdominal infections: A study based on the in-vitro surveillance data in China.

BACKGROUND: With the increase in drug resistance rates of pathogens isolated from complicated intra-abdominal infections (cIAIs), ceftazidime/avibactam (CAZ-AVI) is increasingly used clinically. However, given the high drug cost and the fact that not yet covered by the health insurance payment, this study evaluated the cost-effectiveness of CAZ-AVI plus metronidazole versus meropenem as a first-line empiric treatment for cIAIs from the perspective of the Chinese healthcare system. METHODS: A decision analytic model with a one-year time horizon was constructed to assess the cost-effectiveness based on the entire disease course. Model inputs were mainly obtained from clinical studies, published literature, and publicly available databases. Primary outcomes were cost, quality-adjusted life years (QALYs), life years (Lys), and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were also performed. RESULTS: In the base cases, compared to meropenem, CAZ-AVI plus metronidazole had a shorter mean hospital length of stay (-0.77 days per patient) and longer life expectancy (+0.05 LYs and +0.06 QALYs). CAZ-AVI plus metronidazole had an ICER of $25517/QALY, which is well below the threshold of $31509 per QALY in China. The one-way sensitivity analysis showed that the change of the treatment duration of CAZ-AVI plus metronidazole was the parameter that most influenced the results of the ICER. In probabilistic sensitivity analysis, CAZ-AVI plus metronidazole was the optimal strategy in 75% of simulations at $31510/QALY threshold. CONCLUSIONS: CAZ-AVI plus metronidazole could be considered as a cost-effective option for the empiric treatment of patients with cIAIs in China, and this benefit will be more evident when the price of CAZ-AVI decreases by 23.8%.

The impact of high on-treatment platelet reactivity and fibrinogen levels on ischemic events in patients with ST elevation myocardial infarction: a prospective observational study.

BACKGROUND: After treatment, high residual platelet reactivity (HRPR) is considered as an essential risk factor for recurrent ischemic events. AIM: To evaluate the impact of fibrinogen on HRPR after implantation of emergency drug-eluting stents (DES) in patients treated with aspirin and clopidogrel or ticagrelor due to ST-elevation myocardial infarction (STEMI) and to explore the predictive values of HRPR and fibrinogen for adverse ischemic events at 12 months. METHOD: This single-center prospective observational study analyzed patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with second-generation DES implantation from January 2017 to December 2018. Platelet reactivity was measured by thromboelastography (TEG) at 60-72 h after primary PCI. HRPR was defined as the adenosine diphosphate-induced maximum amplitude (MAADP) > 47 mm. RESULTS: A total of 919 patients were analyzed, of which 512 (55.8%) received aspirin and clopidogrel and 406 (44.2%) received aspirin and ticagrelor. Elevated fibrinogen levels were associated with an increased prevalence of HRPR (P < 0.001). High fibrinogen (quartile IV, ≥ 410 mg/dL) was an independent risk factor for HRPR after multivariate regression (odds ratio 6.556, 95% confidence interval [CI]: 3.200-13.431, P < 0.001). When analyzed by Kaplan-Meier survival curves, the combination of high fibrinogen and HRPR was strongly predictive for ischemic major adverse cardiac events at 12 months compared to the group without HRPR and with low fibrinogen (hazard ratio 9.681, 95% CI: 4.467-20.98, log-rank P < 0.001). Similar results were confirmed in subgroups according to different dual antiplatelet therapies. CONCLUSION: A combination of high fibrinogen and HRPR may identify recurrent adverse ischemic events over 12 months. Ticagrelor exhibited more potent platelet inhibition and a better prognosis than clopidogrel.

Effectiveness and safety evaluation of sacubitril/valsartan in blood pressure control and clinical outcomes for elderly patients with heart failure and hypertension: A prospective cohort study.

AIM: This study was conducted to investigate the safety and effectiveness of sacubitril/valsartan (sac/val) for elderly patients with hypertension and heart failure in the real-world setting. METHODS: Patients with established hypertension complicated with structural or functional impairment of ventricular fillings [New York Heart Association (NYHA) functional class II-IV)] were enrolled. The effectiveness of sac/val in terms of BP reduction and improvement in frailty and echocardiographic evaluation of cardiac function were examined from baseline to 6-month administration. RESULTS: Overall, 241 patients were treated with sac/val and 227 with renin angiotensin aldosterone system inhibitor (RAASi) for hypertension control. There were significant difference in the degree of systolic blood pressure reduction between two groups. Echocardiography showed that sac/val significantly improved left ventricular ejection fraction [4.0% (95% CI: 2.0-7.5) vs -1.0 (95% CI: -4.0-2.0), P = 0.001] during the follow-up visits. Significant improvements in NYHA function class and FRAIL scores post sac/val were observed after 3 and 6 month treatment. The rate of primary cardiovascular composite outcome was higher in patients in the RAASi group (26.9%; 95% CI: 19.6-34.0) than in the sac/val group (22.0%; 95% CI: 16.7-27.3). CONCLUSIONS: Sac/val may be useful not only for reducing BP, but also for improving the structural and functional parameters of echocardiography, eventually resulting in a significant improvement of the overall symptomatic status, a significant reduction in NYHA class, and functional improvement.

Correlation between Mean Platelet Volume and Gensini Score in Patients with Coronary Heart Disease in Different Diabetic States.

SUBJECT: To investigate the correlation between mean platelet volume (MPV) levels and Gensini scores in stable coronary heart disease (CHD) patients with or without diabetes. METHODS: A retrospective analysis was conducted on 2525 patients with stable CHD in Zhongshan Hospital, Fudan University. There were 1274 in the low MPV group and 1251 in the high MPV group, divided by a median MPV level of 10.9 fL. In the total population, 1605 patients were non-diabetic and 920 were diabetic. The severity of coronary artery disease was quantified using the Gensini score. RESULTS: The Gensini score was significantly higher in the high MPV group than in the low MPV group (p < 0.001). MPV levels increased significantly with the number of stenotic (>50%) coronary vessels (p < 0.001). The Spearman analysis showed a positive correlation between MPV and Gensini score (r = 0.189, p < 0.001), which was more significant in the diabetic subgroup (r = 0.232, p < 0.001). Receiver operating characteristic (ROC) curves were employed to assess the predictive value of MPV for high Gensini scores, using the median value of 32 points as the cutoff. MPV levels in the diabetes cohort exhibited a higher predictive value for high Gensini scores (area under the curve: 0.635 [0.614-0.657], p < 0.001). Multivariate linear regression analysis showed that diabetes and MPV were independently associated with Gensini scores. CONCLUSION: MPV levels in stable CHD patients can predict the severity of coronary artery stenosis. This correlation is more significant in the presence of diabetes.

Pharmacoeconomic evaluation of isavuconazole, posaconazole, and voriconazole for the treatment of invasive mold diseases in hematological patients: initial therapy prior to pathogen differential diagnosis in China.

Background: Invasive mold diseases (IMD) is associated with high mortality and a substantial economic burden. For high-risk patients, fever drive or diagnostic drive therapy is usually initiated prior to the differential diagnosis of the pathogen. This study evaluated the cost-effectiveness of isavuconazole, posaconazole, vs. voriconazole in the treatment of IMD from the perspective of the Chinese healthcare system, informing healthcare decision-making and resource allocation. Methods: A decision analytic model was constructed using TreeAge Pro 2011 software to evaluate the cost-effectiveness of the entire disease course. We assumed that the prevalence of mucormycosis in the patients entering the model was 7.8%. Efficacy, cost, adverse events, and other data included in the model were mainly derived from clinical studies, published literature, and publicly available databases. The primary outcomes of the model output were total cost, quality-adjusted life years (QALYs), life years (Lys), and incremental cost-effectiveness ratio (ICER). The willing-to-pay (WTP) threshold was defined as one to three times China's GDP per capita in 2022. One-way sensitivity analysis and probability sensitivity analysis were used to determine the robustness of the model. At the same time, the cost-effectiveness of three triazole antifungal agents under a broader range of mucormycosis prevalence, when voriconazole was covered by medical insurance reimbursement, and after the price reduction of posaconazole was discussed. Results: Compared with voriconazole, isavuconazole provided an additional 0.38 Lys (9.29 vs. 8.91 LYs) and 0.31 QALYs (7.62 vs. 7.31 QALYs); ICER was $15,702.46/QALY, well-below the WTP threshold ($38,223/QALY). However, posaconazole did not provide a significant economic advantage over voriconazole (9.40 vs. 9.36 Lys; 7.71 vs. 7.68 QALYs; ICER $64,466.57/QALY). One-way sensitivity analysis found that ICER was highly sensitive to the mortality of patients with invasive aspergillus infection. In the probabilistic sensitivity analysis, when the WTP threshold was $38,223/QALY, the probability of isavuconazole being cost-effective was 72.9%. The scenario analysis results indicated that posaconazole would become cost-effective when the price was reduced by 15% or the prevalence of mucormycosis was 14%. Conclusions: Isavuconazole represents a cost-effective initial option for treating IMD in high-risk hematological patients prior to the differential diagnosis of pathogens. It will also be economical when a 15% reduction in posaconazole cost is achieved.