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BackgroundPediatric thrombosis is a relatively rare but severe condition in the field of pediatrics, with far-reaching consequences. Recent studies have indicated a rising incidence of this disease in children over the years. Additionally, the pharmacological treatment of thrombotic diseases in children faces numerous challenges. Due to significant physiological differences between children and adults, guidelines for the prevention and treatment of thrombotic diseases in adults cannot be directly applied to pediatric patients.PurposeA systematic review of the existing evidence-based medical literature should be conducted to propose pharmacological prevention and treatment recommendations for pediatric thrombotic diseases. Developing a comprehensive and practical pharmacotherapy guideline for the prevention and treatment of pediatric thrombotic diseases is essential to enhancing the rational use of medications in managing these conditions in children.MethodsThe guideline development followed the World Health Organization's (WHO) Handbook for Guideline Development. This involves systematically searching and extensively collecting data on common medication issues in the prevention and treatment of pediatric thrombosis nationwide. The Delphi method was used to survey experts and identify the clinical issues to be included. Subsequently, a systematic literature review was conducted to evaluate existing primary studies, systematic reviews, and guidelines or consensus statements from professional organizations. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The Delphi method was employed again to reach a consensus on the recommendations and evidence levels. This process was culminated in the development of the Guideline for Pharmacological Management of Thrombotic Diseases in Children.ResultsDuring the guideline development process, a total of 29 clinical issues were collected and evaluated by 78 experts in clinical pharmacy and clinical medicine. Through two rounds of surveys, 13 clinical issues were selected. Under the supervision of two methodologists, 13 clinical pharmacotherapy recommendations were formulated.ConclusionBy conducting a comprehensive assessment of the feasibility and safety of clinical practices, the guideline provides specific anticoagulant medication recommendations for pediatric healthcare professionals. This will help enhance the prevention and treatment of pediatric thrombosis, promoting more standardized and effective medical practices.

ObjectiveTo optimize the construction of pharmaceutical services in medical institutions, advance the development of clinical pharmacy as a discipline, enhance the level of clinical pharmacy services, systematically implement and evaluate clinical pharmacy practices, and improve patient therapeutic outcomes, we have developed the Practice Guidelines for the Value Evaluation of Clinical Pharmacy Services (Version 2).MethodsThis guideline was designed following the World Health Organization (WHO) Guideline Development Manual. The Delphi method was employed to identify clinical questions. A comprehensive systematic search was conducted to collect existing evidence on relevant issues, and the systematic reviews, evidence grading, and evidence summaries were subsequently compiled. The guideline employs the Joanna Briggs Institute (JBI) evidence level system from Australia and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system introduced by WHO in 2004 to classify the quality of evidence. Consensus on the recommendations and evidence levels was achieved through the Delphi method, resulting in the formation of the Practice Guidelines for the Value Evaluation of Clinical Pharmacy Services (Version 2).ResultsThrough a questionnaire survey of over 100 experts and the Delphi method voting, 23 preliminary indicators for evaluating the value of clinical pharmacy services were identified. The content of these included indicators was searched according to the PICO principle, followed by systematic reviews, meta-analyses, network meta-analyses, and related original research. Each search strategy was reviewed and approved by the guidelines steering committee. Ultimately, three dimensions for evaluating the value of clinical pharmacy were identified, encompassing 15 indicators, resulting in 20 recommendations.ConclusionThis guideline presents a set of metrics to assess the quality and effectiveness of clinical pharmacy services, which is crucial for enhancing and elevating clinical pharmacy services in healthcare institutions.Systematic review registrationhttp://www.guidelines-registry.org/guide/28502a74-7038-439c-bdee-d355747e2a9d, identifier: PREPARE-2022CN756.

Abstract This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off‐pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first‐time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple‐electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log‐rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate‐stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p

Background: Thromboembolic disease is associated with a high rate of disability or death and gravely jeopardizes people’s health and places considerable financial pressure on society. The primary treatment for thromboembolic illness is anticoagulant medication. Fondaparinux, a parenteral anticoagulant medicine, is still used but is confusing due to its disparate domestic and international indications and lack of knowledge about its usage. Its off-label drug usage in therapeutic settings and irrational drug use are also common.Objective: The aim of this guideline is to enhance the judicious clinical application of fondaparinux by consolidating the findings of evidence-based research on the drug and offering superior clinical suggestions.Methods: Seventeen clinical questions were developed by 37 clinical pharmacy experts, and recommendations were formulated under the supervision of three methodologists. Through methodical literature searches and the use of recommendation, assessment, development and evaluation grading techniques, we gathered evidence.Results: This guideline culminated in 17 recommendations, including the use of fondaparinux for venous thromboembolism (VTE) prevention and treatment, perioperative surgical prophylaxis, specific diseases, special populations, bleeding and overdose management. For different types of VTE, we recommend first assessing thrombotic risk in hospitalized patients and then administering the drug according to the patient’s body mass. In surgical patients in the perioperative period, fondaparinux may be used for VTE prophylaxis, but postoperative use usually requires confirmation that adequate hemostasis has been achieved. Fondaparinux may be used for anticoagulation prophylaxis in patients hospitalized for oncological purposes, in patients with atrial fibrillation (AF) after resuscitation, in patients with cirrhosis combined with portal vein thrombosis (PVT), in patients with antiphospholipid syndrome (APS), and in patients with inflammatory bowel disease (IBD). Fondaparinux should be used with caution in special populations, such as pregnant female patients with a history of heparin-induced thrombocytopenia (HIT) or platelet counts less than 50 × 109/L, pregnant patients with a prethrombotic state (PTS) combined with recurrent spontaneous abortion (RSA), and children. For bleeding caused by fondaparinux, dialysis may partially remove the drug.Conclusion: The purpose of this guideline is to provide all healthcare providers with high-quality recommendations for the clinical use of fondaparinux and to improve the rational use of the drug in clinical practice. Currently, there is a lack of a dedicated antidote for the management of fondaparinux. The clinical investigation of activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFⅦa) as potential reversal agents is still pending. This critical gap necessitates heightened scrutiny and research emphasis, potentially constituting a novel avenue for future inquiries into fondaparinux sodium. A meticulous examination of adverse events and safety profiles associated with the utilization of fondaparinux sodium will contribute significantly to a more comprehensive understanding of its inherent risks and benefits within the clinical milieu.

Background: venous thromboembolism (VTE) is one of the most common complications after major orthopaedic surgery. Recent studies have suggested that aspirin may also be effective in preventing VTE, but it is still controversial whether it can be routinely used.Objectives: To compare the efficacy and safety of aspirin against oral anticoagulants in the prevention of VTE following total hip arthroplasty (THA), total knee arthroplasty (TKA) or hip fracture surgery (HFS).Methods: Relevant publications have been obtained using electronic search databases such as PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials. gov. from inception to 20 July 2023. Only RCTs evaluating the efficacy and safety of aspirin compared with oral anticoagulants undergoing major orthopaedic surgery were included in the meta-analysis. The primary outcome reported was any VTE event (including deep vein thrombosis (DVT) and pulmonary embolism (PE)). Secondary outcomes included mortality, major bleeding (including gastrointestinal bleed, cerebrovascular hemorrhage, or any bleeding requiring a return to the theater), minor bleeding (ecchymosis, epistaxis, hematuria), and wound complications. The risk of bias for all included studies was assessed according to the Cochrane Collaboration’s tool.Results: After screening 974 studies, 12 randomized clinical trials (RCTs) were included, involving 5,088 participants, including 2,540 participants in aspirin, 2,205 participants in rivaroxaban, and 323 participants in warfarin. Aspirin was found to be less effective than oral anticoagulants in thromboprophylaxis after major orthopedic surgery (RR = 1.206, 95% CI 1.053–1.383). After subgroup analysis according to the type of oral anticoagulant, the results showed that aspirin was similar to rivaroxaban and inferior to warfarin. Considering that the studies in the warfarin group were all conducted before 2000, our results need to be further confirmed. In addition, the aspirin group had a higher risk of VTE than the control group in other subgroups, including a follow-up time of ≤3 months, type of procedure as TKA, high-dose aspirin (≥650 mg qd), and no combined use of mechanical prophylaxis. In terms of safety events, aspirin did not show significant differences in major bleeding (RR = 0.952, 95% CI 0.499–1.815), all-cause mortality (RR = 1.208, 95% CI 0.459–3.177), and wound-related events (RR = 0.618, 95% CI 0.333–1.145) compared with oral anticoagulants, and aspirin was associated with a reduction in the risk of minor bleeding (RR = 0.685, 95% CI 0.552–0.850) events and total bleeding (RR = 0.726, 95% CI 0.590–0.892).Conclusion: Aspirin reduces bleeding risk after major orthopedic surgery compared with oral anticoagulants, but may sacrifice VTE prevention to some extent. Updated evidence is needed to analyze the thromboprophylaxis effects of aspirin in patients undergoing major orthopedic surgery.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=463481, identifier CRD42023463481.

IntroductionThe guidelines' recommendations for anticoagulation in cancer patients with catheter-related thrombosis are unclear. The aim of this systematic review was to assess anticoagulation management in cancer patients with catheter-related thrombosis (CRT) based on previously published studies.MethodsAs of June 10, 2023,we searched databases including PubMed, Embase, and Cochrane and included 11 observational studies that met the criteria. We evaluated 770 adults with active cancer and objectively confirmed patients with CRT who were using drugs including warfarin, LMWH, and new oral anticoagulants as antithrombotic therapy.ResultsWe extracted outcome data, including thrombosis recurrence, catheter dysfunction, major bleeding, and death, and performed a meta-analysis.DiscussionIn this study we found that the risk of VTE recurrence was higher with rivaroxaban, the risk of bleeding and death appeared to be greater with warfarin, and although the risk of catheter dysfunction due to LMWH is a concern, it is still a more reasonable option for cancer patients with catheter-related thrombosis.Systematic Review Registrationhttp://www.clinicaltrials.gov, identifier (CRD42022367979).

Soluble guanylate cyclase agonists and guanylate cyclase C agonists are two popular drugs for diseases of the cardiovascular system and digestive systems. The common denominator in these conditions is the potential therapeutic target of guanylate cyclase. Thanks to in-depth explorations of their underlying signaling mechanisms, the targets of these drugs are becoming clearer. This review explains the recent research progress regarding potential drugs in this class by introducing representative drugs and current findings on them.

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and the response rate and survival rate of many cancers have also been improved. Despite the success of immune checkpoint inhibitors, resistance limits the number of patients who can achieve a lasting response, and immune-related adverse events complicate treatment. The mechanism of immune-related adverse events (irAEs) is unclear. We summarize and discuss the mechanisms of action of immune checkpoint inhibitors, the different types of immune-related adverse events and their possible mechanisms, and describe possible strategies and targets for prevention and therapeutic interventions to mitigate them.

Context Re-yan-ning mixture (RYNM) is a new national drug approved by China's State Food and Drug Administration for the treatment of colds, simple pneumonia and acute bronchitis. Objective To determine the mechanism of action of RYNM in the treatment of bacterial pneumonia. Materials and methods Using the network pharmacology approach, the multiple components, component candidate targets and multiple therapeutic targets of RYNM were screened and functionally enriched. Also, we established a rat Streptococcus pneumonia model to verify the results of network pharmacology enrichment analysis. Forty male SPF Sprague Dawley rats were divided into four groups of 10 rats: control (normal saline), model (normal saline), levofloxacin-intervened and RYNM-intervened groups. IL-10, NOS2, COX-1, IL-6, TNF-α and NF-κB in serum and BALF were detected by ELISA. Western blot detected IL-17, IL-6, TNF-α, COX-2 and Bcl-2. Results The network pharmacology approach successfully identified 48 bioactive components in RYNM, and 65 potential targets and 138 signal pathways involved in the treatment of Streptococcus pneumonia with RYNM. The in vivo experiments indicated that model group has visible inflammation and lesions while RYNM and levofloxacin groups have not. The RYNM exhibited its therapeutic effects on Streptococcus pneumonia mainly via the regulation of cell proliferation and survival through the IL-6/IL-10/IL-17, Bax/Bcl-2, COX-1/COX-2, NF-κB and TNF-α signalling pathways. Discussion and conclusions The present study demonstrated the protective effects of RYNM on Streptococcus pneumonia, providing a potential mechanism for the treatment of bacterial pneumonia with RYNM.

Background: Combination therapy has become an attractive option in pulmonary arterial hypertension (PAH) treatment. The aim of this study was to investigate whether additional use of prostacyclin analogs could exert any additional benefits over background targeted therapies in PAH patients.Methods: Searches were performed on PubMed, Embase, and ClinicalTrials.gov from inception to 1 October 2021. Randomized controlled trials were included if patients had been treated with prostacyclin analog-containing combination therapy and compared with the use of other PAH-specific background therapies. The bias risk and statistical analysis of the enrolled studies were performed with RevMan 5.1. Sensitivity analysis and funnel plot were used to evaluate the stability and publication bias, respectively. PROSPERO registered number CRD42021284196.Results: Ten trials involving 1828 patients were included. Prostacyclin analog treatment was associated with greater improvement in clinical worsening (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.57–0.86), 6-min walk distance (mean difference [MD], 37.17 m; 95% CI, 3.01–71.33 m), NYHA/WHO functional class (RR, 1.58; 95% CI, 1.21–2.05), mean pulmonary artery pressure (MD, −9.23 mmHg; 95% CI, −17.44 to −1.03 mmHg), and cardiac index (MD, 0.41 L/min/m2; 95% CI, 0.26–0.55 L/min/m2) than the control group. No significant differences in pulmonary vascular resistance (MD, −137.22 dyn·s/cm5; 95% CI, −272.61 to −1.84 dyn·s/cm5) and all-cause mortality (RR, 0.96; 95% CI, 0.57–1.61) were found between the prostacyclin analog group and control group. Of note, more adverse events (RR, 1.07; 95% CI, 1.02–1.13) occurred in the prostacyclin analog group but no significant increase in serious adverse events (RR, 1.25; 95% CI, 0.75–2.11).Conclusion: Additional prostacyclin analog treatment exerted benefits on clinical worsening, exercise capacity, functional class, mean pulmonary artery pressure, and cardiac index in PAH patients, but it was associated with overall risk of adverse events.Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284196, identifier CRD42021284196.

Background: Alpha-fetoprotein-negative (p = 0.009), tumor capsule (HR = 0.392, p = 0.017), rim enhancement (HR = 2.825, p = 0.002) and TTPVI (HR = 5.511, p < 0.001) were independent predictors for early recurrence of AFP-NHCC patients. The nomogram integrated these independent predictors and achieved better predictive performance with AUCs of 0.89 and 0.85 in the training and validation datasets, respectively. The calibration curve and decision curve analysis both demonstrated better predictive efficacy and discriminative ability of the nomogram. Conclusions: The nomogram based on the multivariable Cox proportional hazards regression analysis presented accurate individual prediction for early recurrence of AFP-NHCC patients after surgery. This nomogram could assist physicians in personalized treatment decision-making for patients with AFP-NHCC.