Risultati per: Gestione del dolore post-operatorio

Circulation, Volume 150, Issue Suppl_1, Page A4145353-A4145353, November 12, 2024. Background:Myocardial injury complicating percutaneous coronary intervention (PCI) is associated with mortality, but sex differences in outcomes are uncertain. We explored sex differences in the incidence and long-term outcomes of post-PCI myocardial injury (PPMI).Methods:Adults who underwent PCI at NYU between 2011-2020 were included in this retrospective analysis. Patients with ACS as the indication for PCI were excluded. PPMI was defined as a peak CKMB concentration >99% of the upper reference limit. The incidence of PPMI by sex was compared by Chi-square tests. Independent predictors of elevated CKMB post-PCI were evaluated with linear regression models in subgroups by sex. Cox proportional hazard models were generated to evaluate relationships between PPMI and all-cause mortality by sex.Results:Of 10,807 adults undergoing PCI, 24.9% (2,694) were female. Females were older than males at the time of PCI (68.9 vs. 65.8, p

Circulation, Volume 150, Issue Suppl_1, Page A4146071-A4146071, November 12, 2024. Background:Aortic stenosis (AS) and cardiac amyloidosis (CA) frequently coexist. There is a paucity of data on whether the presence of CA impacts post-procedural and clinical outcomes after transcatheter aortic valve replacement (TAVR) among AS patients.Objective:In this analysis, we sought to leverage data from the TriNeTX Global Collaborative Network to determine the impact of CA on mortality and cardiovascular/ischemic outcomes at 1-month and 1-year post-TAVR.Methods:The TriNeTX Global Collaborative Network research database was used to identify patients aged ≥18 years from January 2012 to April 2023. Patients with AS were categorized into two groups: one with CA and having TAVR, and a control group with non CA group having TAVR. Patients were followed for 1 month and 1 year respectively. Propensity score-matched analysis (PSM) (1:1) was performed on age, gender, race, hypertension, diabetes mellitus, and chronic kidney disease. Primary outcome was all-cause mortality (ACM), while secondary outcomes were acute myocardial infarction (AMI), ischemic stroke, ventricular arrhythmias, and major adverse cardiovascular event (composite of ACM, ischemic stroke and AMI).Results:After 1:1 PSM, the study cohort comprised of 351 patients in the CA group and 351 patients in the non-CA group. The mean age of patients in CA and non-CA groups was 79.6 and 79.5 years. PSM analysis showed that ACM was comparable between CA and non-CA group after 1-month (RR, 1.00 (95%CI: 0.42-2.39),P=0.98), and after 1-year follow up (RR, 0.92 (95%CI: 0.59-1.44),P=0.736). AMI was also found comparable between the two cohorts, both after 1-month (RR, 1.189 (95%CI: 0.503-2.811),P=0.693), and after 1-year (RR, 1.288 (95%CI: 0.598-2.773),P=0.516). Similar trends were found for ischemic stroke, ventricular arrhythmias and MACE both after 1-month and 1-year follow up.Conclusion:This study shows that TAVR can be safe to be considered among cardiac amyloidosis patients with aortic stenosis

Circulation, Volume 150, Issue Suppl_1, Page ASu1202-ASu1202, November 12, 2024. Introduction:The TTM2 trial showed that active fever prevention below 37.5°C and hypothermia at 33°C had similar outcomes in out-of-hospital post cardiac arrest patients. However, the patients in the trial had mild hypoxic encephalopathy, and the effects of hypothermia may vary with its severity. We previously reported that amplitude-integrated electroencephalography (aEEG) findings after the return of spontaneous circulation can be used to categorize the severity of hypoxic encephalopathy (Crit Care. 2018;22:226). In September 2022, we adopted a new temperature control protocol wherein the target temperature was set based on aEEG findings. This study examined changes in outcomes before and after implementing this new protocol.Methods:We assessed out-of-hospital cardiac arrest patients who received post cardiac arrest care in our emergency intensive care unit between March 2021 and February 2024. We divided the patients into two groups: before (B) and after (A) the introduction of the new protocol. We classified the patients into categories 1 (C1) to 4 (C4) based on the severity of hypoxic encephalopathy (Figure 1). All patients in group B were treated with hypothermia at 34°C. In group A, patients in C1 were treated with active fever prevention, and those in C2–C4 received hypothermia at 34°C (Figure 2). Primary outcome was favorable neurological outcomes (cerebral performance categories of 1 or 2) at hospital discharge. Secondary outcome was the duration of mechanical ventilation.Results:A total of 160 patients were included. The median age was 62 years and 105 (66%) patients had cardiac etiology. Fifty-five (34%) patients underwent extracorporeal cardiopulmonary resuscitation. The median cardiac arrest time was 29 min. Groups B and A comprised 57 and 103 patients, respectively. C1 category comprised 20 and 28 patients in groups B and A, respectively. The rate of favorable neurological outcomes was 35% in both B and A groups (p=1.00). Regarding C1 patients, the rates were 90% and 86% in B and A groups (p=1.00). Median duration of mechanical ventilation was 5 and 3 days in group B and A, respectively (p=0.11).Conclusion:Neurological outcomes before and after introducing the new protocol were similar. Management of patients with mild hypoxic encephalopathy can be simplified with active fever prevention. A temperature control protocol based on the severity of hypoxic encephalopathy using aEEG findings is feasible for emergency physicians.

Circulation, Volume 150, Issue Suppl_1, Page A4146021-A4146021, November 12, 2024. Background:Heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) is a common comorbidity in patients undergoing transcatheter aortic valve replacement (TAVR). However, post-TAVR outcomes among HFpEF and HFrEF patients have not been well studied.Objective:This study aims to investigate the clinical outcomes post-TAVR among patients with HFrEF vs. HFpEF.Methods:The TriNeTX Global Collaborative Network research database was used to identify patients aged ≥18 years from January 2005 to May 2023. Patients were categorized into two groups: HFpEF and a control group with HFrEF, with both groups of patients undergoing TAVR and followed for 1-month and 1-year. Propensity score-matched analysis (PSM) (1:1) was performed on age, gender, race, body mass index, hypertension, diabetes mellitus, chronic kidney disease, smoking status, hemoglobin level, low density lipid (LDL) level, and various drugs including ACEi, ARBi, beta-blockers, SGLT2i and statins. Primary outcome was all-cause mortality (ACM), while secondary outcomes were acute myocardial infarction (AMI), ischemic stroke, hemorrhagic stroke, major bleeding and major adverse cardiovascular event (MACE) (composite of ACM, AMI and ischemic stroke).Results:After 1:1 propensity score matching (Figure 1), the study cohort comprised of 11, 982 patients in HFpEF with TAVR and 11, 982 patients in the control group. The mean age of patients in HFpEF and HFrEF was 81.7 and 81.5 years, respectively. PSM analysis showed that post-TAVR outcomes among HFpEF patients were significantly associated with lower risk of ACM after 1-month (RR, 0.88 (95%CI: 0.707-0.953),P=0.009), and after 1-year (RR, 0.93 (95% CI: 0.87-0.99),P=0.041) compared with the HFrEF group. A similar trend was observed with a significant reduction in the risk of MACE after 1-month (RR, 0.86, (95% CI: 0.74-0.99),P=0.043), however, it was non-significant after 1-year (RR, 0.942 (95% CI: 0.881-1.007),P=0.077). However, the risk of AMI, ischemic stroke, hemorrhagic stroke, major bleeding both at 1-month and 1-year follow up were comparable between the HFpEF and HFrEF post-TAVR.Conclusion:In patients with HFpEF post-TAVR, there was a significant decrease in ACM at 1-month and 1-year, while there was a significant reduction in MACE only at 1-month. Further investigation is warranted to determine whether HFpEF has better clinical outcomes than patients with HFrEF.

Circulation, Volume 150, Issue Suppl_1, Page A4118018-A4118018, November 12, 2024. Introduction:Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated.Methods:Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. Outcomes were PTM and hematologic malignancy (either leukemia, lymphoma or post-transplant lymphoproliferative disorder). Multivariable Fine-Gray competing-risk regression adjusting for age, sex, race, prior cardiac surgery, smoking, diabetes, induction immunosuppression, recipient and donor cytomegalovirus and Ebstein-Bar virus status was used to estimate subhazard ratio (SHR).Results:Of the total of 29,717 patients with HT were included, 1,017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and more likely to have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with higher risk of PTM (aSHR 1.44, 95% CI 1.15 – 1.80) and hematologic malignancy (aSHR 2.09, 95% CI 1.28 – 3.42). Among patients < 45 years old, CHD had an unadjusted SHR of 1.55 (95% CI 1.11 – 2.16) of PTM, Figure.Conclusions:Among adult patients with HT, CHD was associated with increased risk of PTM and hematologic malignancy. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

Circulation, Volume 150, Issue Suppl_1, Page A4146947-A4146947, November 12, 2024. Background:The prevalence of both obesity and the use of left ventricular assist devices (LVAD) is increasing in pediatrics, but what impact obesity has on post-heart transplant (HT) outcomes when using an LVAD as a bridge to transplant (BTT) is unknown.Methods:Retrospective cohort study of patients 12-18 years old in the UNOS database with a durable LVAD and listed for heart transplant (HT) between 7/1/2004-12/31/2021. Demographic and clinical variables were assessed. Patients were classified as overweight (BMI≥85-

Circulation, Volume 150, Issue Suppl_1, Page A4144199-A4144199, November 12, 2024. Background:The current standard for children diagnosed with rheumatic heart disease (RHD) is secondary antibiotic prophylaxis (SAP) for at least 10 years or to a minimum age of 21. However, these recommendations were developed prior to the widespread use of echocardiography and based largely on expert opinion. A recent clinical trial in Uganda found that up to 50% of children with early RHD show echocardiographic normalization by 2 years. More research is needed to understand if continued SAP is needed after echocardiographic normalization.Hypothesis:There is a low risk of RHD recurrence in individuals who have had normalization of their echocardiogram following early RHD diagnosis.Aim:To determine the 2-year safety of not providing SAP to children and adolescents with early RHD who have shown echocardiographic normalization.Methods:The GOAL trial in Uganda, 2018-2021, compared SAP with Benzathine Penicillin G (BPG) to no prophylaxis among children with early RHD. GOAL-Post is a non-randomized prospective extension study of the GOAL Trial. Children with echocardiographic normalization at the end of GOAL, regardless of treatment arm, were followed prospectively without SAP, for 2 additional years. Echocardiograms were performed at the end of follow-up, uploaded to a cloud server, and interpreted by a four-person adjudication panel. Recurrence was determined by side-by-side comparison with GOAL enrollment and completion studies.Results:Of 345 eligible participants, 330 (96%) were enrolled, mean age 16 years (SD = 2.3), 56% female, and all completed the two-year follow-up. Only one of 330 (0.3%) progressed to moderate/severe RHD after the 2 years, and an additional 26 participants (7.9%) had evidence of mild RHD, which was clinically comparable to their cardiac status at the start of the GOAL Trial. No participants had clinical signs or symptoms of RHD and no documented rheumatic fever. This means that 99% of children and adolescents who had echocardiographic normalization were safe from moderate/severe RHD and 92% were safe from any RHD, without SAP.Conclusion:These findings suggest that it may be safe to consider stopping of SAP among children who show echocardiographic normalization, providing more individualized recommendations for SAP duration, rather than the current model of long-term SAP for all. Further study is needed including a stoppage of SAP trial, to generate higher quality evidence for this approach.

Circulation, Volume 150, Issue Suppl_1, Page A4134630-A4134630, November 12, 2024. Background:Over 3 million percutaneous coronary interventions (PCI) are performed yearly to treat coronary artery stenosis. Stent thrombosis is a catastrophic complication associated with high morbidity and mortality, and its prevention requires the use of prolonged dual antiplatelet therapy (DAPT), which increases bleeding risk. Within the first 30 days after PCI, the mortality of DAPT-associated major bleeding is on par with recurrent myocardial infarction.Research question:No stent system that provides focal antiplatelet activity to prevent stent thrombosis exists, eliminating the need for systemic DAPT and subsequent bleeding risk.Aim:To address this unmet need, we have developed such a stent, termed “the ticagrelor coated stent” (TCS).Methods:Self-assembled monolayers (SAMs) of 12-aminododecylphosphonic acid (ADPA) were formed on cobalt-chromium stents. The amine tail group of ADPA was used to link the ticagrelor molecule through a Mitsunobu reaction and confirmed via infrared spectroscopy. Coating uniformity was validated via atomic force microscopy. In an ex-vivo porcine arterio-venous fistula model, the ticagrelor-coated stents (TCS) were placed in alternating series adjacent to uncoated bare metal stents (BMS). Similarly, TCS and everolimus-eluting stents were placed in the porcine left circumflex arteries for acute (7 days) and chronic (35 days) studies.Results:(Figure 1): Grossly, no thrombus was seen on the TCS compared to the BMS. Platelet and micro-thrombi adherence were significantly reduced on TCS. Notably, inflammation, measured by neutrophil and monocyte adherence, was also reduced by approximately 10-fold on the TCS vs the BMS. Angiography, optical coherence tomography (OCT), and histopathology results show the TCS widely patent without systemic DAPT.Conclusion:These findings show that TCS prevents stent thrombosis through focal anti-platelet action and may reduce the bleeding risk associated with prolonged use of systemic DAPT. Long-term safety and efficacy studies are underway.

Circulation, Volume 150, Issue Suppl_1, Page A4141879-A4141879, November 12, 2024. Background:Current guidelines recommend oral anticoagulation (OAC) for at least two months post-radiofrequency ablation (RFA) in all patients with atrial fibrillation (AF). The endothelial injury during RFA that can promote thrombus formation, does not happen in pulsed-field ablation (PFA).Objective:We evaluated the optimal duration of OAC therapy needed for effective stroke prevention following PFA.Methods:Consecutive patients undergoing PFA for AF were included in the study and prospectively followed-up for 1 year. Based on the duration of post-ablation OAC [non-vitamin K OAC (NOAC)] therapy they were classified intogroup 1:NOAC for 1 month and group 2: NOAC for ≥2 months. Patients were closely monitored for thromboembolic (TE) events via telemedicine. Stroke/transient ischemic attacks that occurred while the patients were in full compliance with the anti-thrombotic therapy, were counted as the reportable TE events.Results:A total of 120 patients were included in this analysis. The mean age of the study population was 59.80 ± 16.39 years; 70 (58%) were male and the CHA2DS2-VASc score was 4.27 ± 1.22. Mean number of PFA applications given was 76.64 ± 36.04.Group 1included 49 (40.8%) andgroup 2was comprised of 71 (59.2%) patients. Baseline characteristics were comparable between the groups.At 1 year,no stroke or transient ischemic attacks were reported in group 1 and 2. At that time point, 42 (85.7%) and 60 (84.5%) patients were arrhythmia-free in group 1 and 2 respectively (p=0.85).Conclusion:In this series of patients, OAC could be safely discontinued after 1 month following the PFA procedure. Thus, it seems redundant to continue OAC beyond 1 month after PFA.

Circulation, Volume 150, Issue Suppl_1, Page ASu1101-ASu1101, November 12, 2024. Introduction:Bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use are interventions that can increase survival rates of out-of-hospital cardiac arrests (OHCA). However, willingness and comfort levels of such interventions amongst laypersons vary greatly, especially in racial and ethnic minoritized groups including African Americans and Hispanics.Research Question:To assess the comfort level and perceived barriers of participants before and after community-based CPR and AED education.Methods:We conducted a family-centered quasi-experimental study in primarily Black and Hispanic churches around the Will and Dupage counties of Illinois. Informed consent was obtained. Participants watched an instructor-facilitated CPR and AED 10-minute educational video. Comfort levels pre- and post-training were assessed on a scale of 1 (least confident) to 5 (extremely confident) and reported as percentages. A semi-structured questionnaire was used to assess perceived barriers to performing CPR.Results:Out of 27 participants who completed training assessment, majority were females 55.6% (n=15), with 44.4% (n=12) males; 66.7% (n=18) African Americans, and 33.3% (n=9) Hispanic or Latino. 70.4% (n=19) of the participants spoke English while 29.6% (n=8) spoke Spanish. Before training, 73% (n=19) and 81% (n=21) of participants were not confident in administering CPR or using AED respectively on someone in cardiac arrest. After training, confidence level increased to 100% for both CPR and AED use. Perceived barriers to CPR prior to training included participants not knowing how to perform CPR correctly (65%), concern that they may further harm someone (4%), concerns about potential legal liability (4%), and loss of recall on how to perform CPR (4%), while 23% had no barrier.Conclusion:Comfort levels of individuals performing CPR and AED use increased significantly after community-based CPR and AED education. Data collection is ongoing to assess comfort level with a larger number of participants. Implementing community-based CPR training in churches allows for community-oriented CPR trainings and may help improve bystander comfort level and willingness to perform CPR during OHCA, especially in minoritized communities.

Circulation, Volume 150, Issue Suppl_1, Page A4139840-A4139840, November 12, 2024. Background:sodium-glucose cotransporter 2 inhibitors (SGLT2i) , a new type of oral hypoglycemics agent used to treat type 2 diabetes, have a positive effect on the progression of heart failure, but there is a concern with the association between SGLT2i and acute kidney injury (AKI).Materials and Methods:We retrospectively evaluated consecutive patients undergoing CABG surgery from January 2018 to December 2021 in the hospital. A cohort of patients who had been prescribed SGLT2i was identified and matched by propensity score with a cohort of patients who had not been prescribed SGLT2i in a ratio of 1:3. The primary outcome was AKI following CABG. Furthermore, a meta-analysis was conducted on the relationship between SGLT2i and acute kidney injury (AKI). Four studies, comprising a total of 25,116 patients, were included in the analysis.Results:A total of 403 patients who had received SGLT2i and 1209 without SGLT2i were included in the analysis. AKI was observed in 54 patients (13.4%) in the SGLT2i group and 373 patients (30.9%) in the non-SGLT2i group following CABG. The SGLT2i exhibited a lower incidence of AKI compared with the non-SGLT2i (P < 0.001). The findings of the meta-analysis indicated that SGLT2i was associated with a decreased incidence of AKI (P < 0.001; OR= 0.525, [95% CI, (0.437-0.631]).Conclusion:The results of our prospective study indicated a reduced risk of AKI in patients undergoing CABG and were treated with SGLT2i.

Circulation, Volume 150, Issue Suppl_1, Page A4144823-A4144823, November 12, 2024. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) have become a significant healthcare burden. Sustained increases in prothrombotic markers have been reported in hospitalized acute COVID-19 patients. However, whether patients with less severe acute infection also endure a persistent prothrombotic state remains uncertain. We tested for a prothrombotic state in this cohort and examined potential mediators. We enrolled 70 adult patients with prior mild acute SARS-CoV-2 infection and sustained PASC symptoms (per WHO criteria). A control healthy group matched for age and sex was also enrolled who were not previously diagnosed with COVID-19. Markers of platelet activation and platelet-neutrophil aggregates (PNA) were quantified using whole-blood flow cytometry. Markers of extracellular traps (citrullinated histones [H3Cit] and cell-free DNA [cfDNA]), anti-dsDNA IgG, and thrombin generation potential were measured in plasma. At recruitment (6 weeks to 3 years post infection), there was increased potential for thrombin generation in the plasma from PASC compared to control reflected by increased peak and velocity index (P

Circulation, Volume 150, Issue Suppl_1, Page A4145489-A4145489, November 12, 2024. Introduction:Pulmonary Arteriovenous Malformations (PAVMs) are a main surgical complication of second-stage palliative Glenn shunt for single ventricle. PAVMs lead to early mortality. Currently there is no available treatment as its physiopathology remains unknown.Hypothesis:This study hypothesizes that hepatic-derived factor causing PAVMs could be proteome-derived.Goals:To discern differences in proteomic profiles of patient-paired serum from superior vena cava (SVC) and hepatic vein (HV) as a preliminary approach to identify PAVM-related hepatic vein blood-enriched factors.Methods:Paired full blood samples were collected from SVC and HV origin during routine cardiac catheterization of patients with diverse cardiac congenital malformations from 0 to 1 years of age (n=3). Serum was extracted and high abundant proteins were depleted. Single-pot solid-phase-enhanced sample preparation method and trypsinization digestion coupled with label-free data-dependent acquisition liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed. Subgroup differential expression analysis by abundance ratio (SVC/HV) (Adj. P-Value

Circulation, Volume 150, Issue Suppl_1, Page A4140722-A4140722, November 12, 2024. Background:Racial disparities have been well described in cardiovascular disease. However, the impact of race on the outcomes post atrial fibrillation (AF) ablation is not well understood.Objective:This study aim to investigate the clinical outcomes post AF ablation among Black and White patients.Method:The TriNeTX Global Collaborative Network database was used to identify patients aged ≥18 years of age from January 2000 to April 2023 which included atrial fibrillation post-ablation patients. Patients were categorized into two groups, one with Black or African American race and another with White race groups. Both groups were followed for 12 months. We used the international Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify comorbidities, and ICD-10 Procedure coding system for procedures. Propensity score-matched analysis (PSM) (1:1) was performed on age, gender, BMI, smoking, hypertension, diabetes mellitus, chronic kidney disease, hemoglobin level and left ventricular ejection fraction. The primary outcome was all-cause mortality (ACM), while secondary outcomes were ischemic stroke, hemorrhagic stroke, acute myocardial infarction (AMI), MACE (composite of ACM, heart failure, AMI, and ischemic stroke) and heart failure (HF).Result:After 1:1 propensity score matching, the study cohort comprised 10, 335 Black patients and 10,335 White patients. The mean age of patients was comparable between both groups (65.2 and 64.9 years). Post ablation, Black patients were having a significantly higher risk of ACM (RR 1.131, 95% CI: 1.002-1.277), HF (RR 1.473, 95% CI: 1.290-1.683), AMI (RR 1.312, 95% CI: 1.117-1.342), and MACE (RR 1.416, 95% CI: 1.250-1.603) as compared with white population. However, the risk of ischemic stroke (RR 1.069, 95% CI: 0.878-1.301) and hemorrhagic stroke (RR 1.466, 95% CI: 0.908-2.369) were found comparable between Black and White patients post ablation.Conclusion:These findings suggest that Black patients post AF ablation were having a higher risk of mortality and MACE.

Objective
The collection of comprehensive data from post-authorisation trials for conditionally authorised anticancer medicines is frequently delayed. This raises questions about the feasibility of post-authorisation randomised controlled trials (RCTs) that aim to address remaining uncertainties. Therefore, this study explored factors that facilitate or impede the feasibility of post-authorisation RCTs from the perspective of stakeholders directly involved in the design, medical-ethical approval, and conduct of these RCTs.

Design
We conducted four qualitative focus groups (FGs).

Setting
FG discussions focused on the oncology setting in European context.

Participants
Twenty-eight European patients, physicians, medical ethicists and pharmaceutical industry representatives participated in the FGs.

Intervention
Respondents were informed about the topic and the purpose of the FGs before and at the start of FG discussions. An FG script was used to guide the discussion, which was informed by 14 semi-structured interviews with various stakeholders.

Results
We identified factors with the potential to impact feasibility related to trial design, trial conduct, factors external to a trial and post-authorisation interaction with regulators. Factors that may be particularly relevant for the post-authorisation setting include the choice of relevant endpoints and the inclusion of a fair comparator (trial design), strategies to increase patients’ and physicians’ willingness to participate (trial conduct), and external factors relating to a medicine’s commercial availability, the presence of competing medicines and trials and the perceptions about clinical equipoise. Post-authorisation interaction with regulators about how to obtain comprehensive data was deemed necessary in cases where a post-authorisation RCT seems infeasible.

Conclusions
Based on the identified factors, our findings suggest that patient recruitment and retention could be assessed more in-depth during regulatory feasibility assessments at the time of granting conditional marketing authorisation and that sponsors and regulators should better inform patients and physicians about the remaining uncertainties for conditionally authorised medicines and the necessity for post-authorisation RCTs. By enhancing the evaluation of trial feasibility, timely completion of post-authorisation RCTs may be facilitated to resolve the remaining uncertainties within a reasonable timeframe.