Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. METHODS: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. RESULTS: A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). CONCLUSIONS: This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.

Prescribing Trends of Oral Anticoagulants from 2010 to 2020 in Shanghai, China: A Retrospective Study.

AIM: Non-vitamin K antagonist oral anticoagulants (NOACs) were developed as an alternative to warfarin to prevent thromboembolism in patients with atrial fibrillation (AF), prosthetic heart valves, venous thromboembolism (VTE), or other thrombotic disorders. The aim of this study is to explore the trends in prescribing OACs, including warfarin and NOACs, in Shanghai, China. METHODS: Prescription data of OACs were retrospectively collected from Rx Analysis System from 2010 to 2020 in Shanghai, China. Comparisons were made on the trends of each OACs according to different indications, age groups, and hospital grades. The costs and the contribution of individual OACs were also explored. RESULTS: Growing trends in overall prescriptions for OACs were observed. The prescriptions of NOACs were significantly increased since 2016, while the prescriptions of warfarin kept decreasing since 2017. A highly statistically significant increase in prescriptions of Rivaroxaban was observed from 2016 to 2020 (P < .001). Despite the price reduction of rivaroxaban in 2018, the total cost of rivaroxaban continued to rise (P < .001). Rivaroxaban emerged as a preferred NOAC in both indications of AF and VTE, and accounted for more than three-quarters of the total costs for OACs since 2019. Compared with rivaroxaban, the prescription numbers of dabigatran and apixaban were much smaller, and the growth of prescriptions were much slower. Differences in prescribing patterns in different indications, age groups, and grades of hospitals were also founded. CONCLUSION: There has been a rapid increase in the use of OAC over the last 11 years in Shanghai, China. NOACs have been adopted rapidly, and have been gradually replacing warfarin. Warfarin remains the top choice for certain patients with valvular heart disease. Future studies are warranted considering changes in the OAC use in a larger scale, as well as the rationality and its influence factors on OAC use.

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system.

Background: With the increased use of immune checkpoint inhibitors (ICIs) in advanced lung cancer, adverse events (AEs), particularly immune-related AEs (irAEs), have garnered considerable interest. We conducted a comprehensive assessment of the toxicity profile in advanced lung cancer using multi-source medical data. Methods: First, we systematically searched the PubMed, Embase, and Cochrane Library databases (from inception to 10 August 2021) for relevant randomised controlled trials (RCTs) involving ICI-based treatments for advanced lung cancer. The primary outcomes were treatment-related AEs and irAEs, including events that were assigned grade 1-5 and 3-5. The secondary outcomes were grade 5 AEs and irAEs (grade 1-5 and grade 3-5) in specific organs. Network comparisons were conducted for 11 treatments, including chemotherapy (CT), ICI monotherapy (three regimens: programmed death-1 receptor [PD-1] inhibitors, programmed death ligand-1 [PD-L1] inhibitors, and cytotoxic T lymphocyte-associated antigen [CTLA-4] inhibitors), dual-ICI combination therapy (two regimens), and treatment using one or two ICI drugs administered in combination with CT (five regimens). We also conducted a disproportionality analysis by extracting reports of various irAEs associated with ICIs from the FDA Adverse Event Reporting System (FAERS) database. The reporting odds ratios and fatality proportions of different irAEs were calculated and compared. PROSPERO: CRD42021268650. Findings: Overall, 41 RCTs involving 23,121 patients with advanced lung cancer were included. Treatments containing chemotherapy increased the risk of treatment-related AEs compared to ICI-based regimens without chemotherapy. Concerning irAEs, PD-L1 + CTLA-4 + CT was associated with the highest risk of grade 1-5 irAEs, followed by two regimens of dual ICI combination, three regimens of ICI monotherapy, and three regimens of one ICI combined with CT. For 3-5 irAEs, CTLA-4 accounted for most AEs. Detailed comparisons of ICI-based treatment options provided irAE profiles based on specific organs/systems and AE severity. Insights from the FAERS database revealed that signals corresponding to pneumonitis, colitis, thyroiditis, and hypophysitis were observed across all ICI regimens. Further analyses of the outcomes indicated that myocarditis (163 of 367, 44.4%), pneumonitis (1610 of 4497, 35.8%), and hepatitis (290 of 931, 31.1%) had high fatality rates. Interpretation: Included RCTs showed heterogeneity in a few clinical factors, and reports derived from the FAERS database might have involved inaccurate data. Our results can be used as a basis for improving clinical treatment strategies and designing preventive methods for ICI treatment in advanced lung cancer. Funding: This study was supported by the Research Project of Drug Clinical Comprehensive Evaluation and Drug Treatment Pathway (SHYXH-ZP-2021-001, SHYXH-ZP-2021-006), Clinical Research Innovation and Cultivation Fund of Ren Ji Hospital (RJPY-LX-008), Ren Ji Boost Project of National Natural Science Foundation of China (RJTJ-JX-001), and Shanghai "Rising Stars of Medical Talent" Youth Development Program - Youth Medical Talents - Clinical Pharmacist Program (SHWJRS (2019) 072).

Framework Development for Clinical Comprehensive Evaluation of Drugs-a Study Protocol Using the Delphi Method and Analytic Hierarchy Process.

Measuring the value of drugs to help make health-care decisions is a complex process which involves confronting trade-offs among multiple objectives. Although guidelines have been released for clinical comprehensive evaluation of drugs, refinement is required when considering a specific drug used in a specific disease. In this study, a two-level framework for clinical comprehensive evaluation of drugs will be developed. Six first-level indicators, including safety, efficacy, costs/cost-effectiveness, novelty, suitability, and accessibility will be evaluated according to the Chinese Guideline for Clinical Comprehensive Evaluation of Drugs. The second-level components involved in the framework will be first validated by the Delphi method and subsequently compared with one another to get the index weight based on the Analytic Hierarchy Process (AHP). The scoring criteria of each component in the framework will also be determined by the Delphi method and AHP. The scoring criteria of components representing therapeutic effects will involve both score of therapeutic effects and score of evidence quality. With the evidence of the drug to be evaluated, the score of each component will be obtained according to the established scoring criteria, and the overall comprehensive score value of the drug will be calculated, which will assist the evidence-based decision making.

Incidence and Risk Factors of Postoperative Severe Discomfort After Elective Surgery Under General Anesthesia: A Prospective Observational Study.

PURPOSE: Patient comfort is an important concern in patients receiving surgery, but the seriousness of discomfort during recovery is unknown. We investigated the incidence of postoperative discomfort based on the Standardized Endpoints in Perioperative Medicine initiative for patient comfort, and identified the risk factors. DESIGN: This was a single-center prospective observational study. METHODS: We enrolled adult patients who underwent elective surgery under general anesthesia between July and December 2018 at West China Hospital of Sichuan University (ChiCTR1800017324). The primary outcome was the incidence of postoperative severe discomfort (PoSD), defined as occurring when a patient experienced a severe rating in two or more domains in the six domains in the Standardized Endpoints in Perioperative Medicine initiative on the same day, including rest pain, postoperative nausea, and vomiting, dissatisfaction of gastrointestinal recovery, dissatisfaction of mobilization, sleep disturbance, and recovery. A generalized estimated equation was constructed to find risk factors of PoSD. FINDINGS: In total, 440 patients completed the study. The incidence of PoSD was 28% on postoperative day (POD) 1, 13% on POD 2, 9% on POD 3, and 3.6% on both POD 5 and 7. The most common discomfort was serious sleep disturbance, ranging from 43% to 10% in the first week after surgery. Longer operative time (odds ratio [95% confidence interval]: 1.56 [1.19 to 2.05], P = .001), gastrointestinal surgery (5.03[2.08,12.17], P < .001), orthopaedic surgery (3.03 [1.35,6.79], P = .007), ear, nose, and throat (ENT) surgery (3.50 [1.22,10.02], P = .020) and postoperative complications (1.77 [1.03-3.04], P = .038) were significant risk factors of PoSD. CONCLUSIONS: The incidence of PoSD after elective surgery under general anesthesia is high. Sleep disturbance was the most common problem identified. Anesthesia providers and perianesthesia nurses may need to optimize anesthetic application, combine different anesthesia methods, improve perioperative management, and provide interventions to reduce and to treat discomfort after surgeries.

Learning Impacts of Pretraining Video-Assisted Debriefing With Simulated Errors or Trainees' Errors in Medical Students in Basic Life Support Training: A Randomized Controlled Trial.

BACKGROUND: Previous studies demonstrated that pretraining video-assisted debriefing (VAD) with trainees' errors (TE) videotaped in a skills pretest improved skill learning of basic life support (BLS). However, conducting a pretest and preparing TE video examples is resource intensive. Exposing individual trainee's errors to peers might be a threat to learners' psychological safety. We hypothesized pretraining VAD with simulated errors (SE, performed by actors) might have the same beneficial effect on skills learning as pretraining VAD with TE, but avoid drawbacks of TE. METHODS: Three hundred twenty-two third-year medical students were randomized into 3 groups (the control [C], TE, SE). A videotaped BLS skills pretest was conducted in 3 groups. Then, group C received traditional training with concurrent feedback. Video-assisted debriefing with TE in the pretest or SE was delivered in groups TE or SE, respectively, followed by BLS training without any feedback. Basic life support skills were retested 1 week later (posttest). Students completed a survey to express their preference to TE or SE for VAD in the future. RESULTS: Higher BLS skills scores were observed in groups TE (85.7 ± 7.0) and SE (86.8 ± 7.5) in the posttest, compared with group C (68.7 ± 13.3, P < 0.001). No skills difference was observed between group TE and SE in the posttest. More trainees (65.8%) preferred SE for VAD. CONCLUSIONS: Pretraining VAD with SE had an equivalent beneficial effect as VAD with TE on BLS skills learning in medical students. More trainees preferred SE for VAD with regard to psychological safety.

A comparison of exposure of Glottis using the Airtraq or the Macintosh Laryngoscope in Potentially difficult airway management: A self-controlled clinical trial.

OBJECTIVE: To compare glottis exposure of the same patients with potentially difficult tracheal intubation (PDTI) subjected to Airtraq laryngoscopy and Macintosh laryngoscopy under consciousness and topical anesthesia. METHODS: A total of 147 PDTI patients with American Society of Anesthesiologists (ASA) I-III were subjected to Airtraq and Macintosh laryngoscopy performed by experienced anesthesiologists under consciousness and topical anesthesia. RESULTS: All patients were successfully intubated. Among them, three patients were intubated with fiberoptic bronchoscopy, 13 with Macintosh laryngoscopy and 131 with Airtraq laryngoscopy. Of the patients with Cormack and Lehance (C&L) Grade-I glottic view, 88 were subjected to Airtraq laryngoscopy and five to Macintosh laryngoscopy; Of the patients with C&L Grade-II glottic view, 56 were subjected to Airtraq laryngoscopy and 21 to Macintosh bronchoscopy; Of the patients with C&L Grade-III glottic view, three were subjected to Airtraq laryngoscopy and 112 to Macintosh bronchoscopy; Of the patients with C&L Grade-IV glottic view, none was subjected to Airtraq laryngoscopy and 9 to Macintosh laryngoscopy. CONCLUSIONS: Airtraq laryngoscopy could significantly improve the glottis exposure and reduce the difficulty of intubation for patients with potentially tracheal intubation compared to the traditional Macintosh laryngoscopy.

Effectiveness and Safety of a Novel Approach for Management of Patients with Potential Difficult Mask Ventilation and Tracheal Intubation: A Multi-center Randomized Trial.

BACKGROUND:: Patients with potential difficult mask ventilation (DV) and difficult intubation (DI) are often managed with awake intubation, which can be stressful for patients and anesthesiologists. This prospective randomized study evaluated a new approach, fast difficult airway evaluation (FDAE). We hypothesized that the FDAE approach would reduce the need for awake intubation. METHODS:: After obtaining informed consent, 302 patients with potential DV/DI undergoing elective surgeries were randomly assigned to the FDAE group (Group E) and the control group (Group C). In Group E, patients were gradually sedated, and adequacy of manual mask ventilation during spontaneous breathing was assessed at various sedation levels. Awake intubation was applied in those with inadequate mask ventilation. In Group C, DI was evaluated under local anesthesia. However, the care team could intubate under general anesthesia if the vocal cords were visible. The primary outcome was the rate of awake intubations in both groups and the induction efficiency assessed by the induction time. The secondary outcome was the incidence of serious complications. RESULTS: The rate of awake intubation was significantly lower in Group E than that in Group C (5.81% vs. 36.05%, χ2 = 42.3, P < 0.001). The induction time was much shorter in Group E than in Group C (11.85 ± 4.82 min vs. 18.71 ± 7.85 min, t = 5.39, P < 0.001). There was no significant difference in the incidence of intubation related complications between the two groups. Patients in Group E had a much lower incidence of recall (9.68% vs. 44.90%, χ2 = 47.68, P < 0.001) of the induction process and higher satisfaction levels than patients in Group C (t = 15.36, P < 0.001). CONCLUSIONS: The FDAE significantly reduces the need for awake intubation and improves the efficiency of the intubation process without comprising safety in patients with potential difficult mask ventilation and DI. TRIAL REGISTRATION:: No. ChiCTR-TRC-11001418; http://www.gctr.org/cn/proj/show.aspx?proj=1562.

Pre-training evaluation and feedback improved skills retention of basic life support in medical students.

BACKGROUND: Pre-training evaluation and feedback have been shown to improve medical students' skills acquisition of basic life support (BLS) immediately following training. The impact of such training on BLS skills retention is unknown. This study was conducted to investigate effects of pre-training evaluation and feedback on BLS skills retention in medical students. METHODS: Three hundred and thirty 3rd year medical students were randomized to two groups, the control group (C group) and pre-training evaluation and feedback group (EF group). Each group was subdivided into four subgroups according to the time of retention-test (at 1-, 3-, 6-, 12-month following the initial training). After a 45-min BLS lecture, BLS skills were assessed (pre-training evaluation) in both groups before training. Following this, the C group received 45 min training. 15 min of group feedback corresponding to students' performance in pre-training evaluation was given only in the EF group that was followed by 30 min of BLS training. BLS skills were assessed immediately after training (post-test) and at follow up (retention-test). RESULTS: No skills difference was observed between the two groups in pre-training evaluation. Better skills acquisition was observed in the EF group (85.3 ± 7.3 vs. 68.1 ± 12.2 in C group) at post-test (p<0.001). In all retention-test, better skills retention was observed in each EF subgroup, compared with its paired C subgroup. CONCLUSIONS: Pre-training evaluation and feedback improved skills retention in the EF group for 12 months after the initial training, compared with the control group.

Pre-training evaluation and feedback improve medical students' skills in basic life support.

BACKGROUND: Evaluation and feedback are two factors that could influence simulation-based medical education and the time when they were delivered contributes their different effects. AIM: To investigate the impact of pre-training evaluation and feedback on medical students' performance in basic life support (BLS). METHODS: Forty 3rd-year undergraduate medical students were randomly divided into two groups, C group (the control) and pre-training evaluation and feedback group (E&F group), each of 20. After BLS theoretical lecture, the C group received 45 min BLS training and the E&F group was individually evaluated (video-taped) in a mock cardiac arrest (pre-training evaluation). Fifteen minutes of group feedback related with the students' BLS performance in pre-training evaluation was given in the E&F group, followed by a 30-min BLS training. After BLS training, both groups were evaluated with one-rescuer BLS skills in a 3-min mock cardiac arrest scenario (post-training evaluation). The score from the post-training evaluation was converted to a percentage and was compared between the two groups. RESULTS: The score from the post-training evaluation was higher in the E&F group (82.9 ± 3.2% vs. 63.9 ± 13.4% in C group). CONCLUSIONS: In undergraduate medical students without previous BLS training, pre-training evaluation and feedback improve their performance in followed BLS training.

In vitro and in vivo evaluation of a novel oral insulin formulation.

AIM: To develop a stable self-emulsifying formulation for oral delivery of insulin. METHODS: Caco-2 cell line and diabetic beagles were used as in vitro and in vivo models to study the absorption mechanism and the hypoglycemic efficacy of the formulation. In addition, various physicochemical parameters of the formulation such as droplet size, insulin encapsulation efficiency and stability were evaluated. RESULTS: This formulation enabled changes in barrier properties of Caco-2 monolayers, as referred by transepithelial electrical resistance (TEER) and apparent permeability coefficients (P(app)) of the paracellular marker ranitidine (20-fold greater than control) but not transcellular marker propranolol, suggesting that the opening of tight junctions was involved. In diabetic beagle dogs, the bioavailability of this formulation was up to 15.2% at a dose of 2.5 IU/kg in comparison with the hypoglycemic effect of native insulin (0.5 IU/kg) delivered by subcutaneous injection. CONCLUSION: This formulation, recently approved by the China State Food and Drug Administration to enter clinical trials, was stable, degradation-protected and absorption-enhanced, and provided a promising formulation for oral insulin delivery.