588 Prognostic impact of early vs. deferred angiography in MINOCA patients

Aims Although an early invasive strategy (coronary angiography performed <24 h) is associated with a lower risk of recurrent/refractory ischaemia among patients with acute myocardial infarction (AMI) and obstructive coronary arteries, the optimal timing of invasive examination in patients with non-obstructive coronary arteries and non-ST-segment elevation presentation (NSTE-MINOCA) has not been explored. This study tested the hypothesis that, compared to early (<24 h) invasive strategy, deferred (≥24 h) coronary angiography has equivalent prognostic impact in patients with NSTE-MINOCA. Methods and results From 2016 to 2020, all consecutive MINOCA patients diagnosed according to the current ESC diagnostic criteria (angiographic conventional cut-off of < 50% coronary stenosis without a clinically apparent alternative diagnosis) and admitted to our Centre with non-ST-segment elevation myocardial infarction (NSTEMI) presentation were enrolled. Very high-risk NSTEMI patients have been excluded from the study. The prognostic value of an early (<24 h) vs. deferred (≥24 h) coronary angiography was assessed. All-cause mortality and a composite endpoint of all-cause mortality, stroke, re-hospitalization for heart failure, and myocardial re-infarction were evaluated. 198 NSTE-MINOCA patients were enrolled. MINOCA patients were more frequently females (64%) and the mean age was 68.6 ± 13.2 years. The median follow-up time was 26 (14–40) months. The total number of events was 54 (27.3%). Kaplan–Meier curves showed that there was no statistically significant difference (P = 0.88) between the two study groups depending on the time of invasive strategy adopted. Specifically, the rates of death (15% vs. 11.3%) and MACEs (28.3% vs. 25%) were similar in MINOCA patients undergoing early vs. deferred angiography. Conclusions We demonstrate for the first time that in the MINOCA population the prognosis was not influenced by an early vs. deferred coronary angiography, unlike in AMI patients with obstructive coronary arteries. These results add another piece to the puzzle and pave the way for the initial use of a non-invasive imaging strategy (e.g. Coronary-CT), mostly in patients with NSTEMI and high clinical suspicion of non-obstructive coronary arteries.

The economic impact of two diagnostic strategies in the management of restorations in primary teeth: a health economic analysis plan for a trial-based economic evaluation

Background Different approaches have been used by dentists to base their decision. Among them, there are the aesthetical issues that may lead to more interventionist approaches. Indeed, using a more interventionist strategy (the World Dental Federation - FDI), more replacements tend to be indicated than using a minimally invasive one (based on the Caries Around Restorations and Sealants—CARS). Since the resources related to the long-term health effects of these strategies have not been explored, the economic impact of using the less-invasive strategy is still uncertain. Thus, this health economic analysis plan aims to describe methodologic approaches for conducting a trial-based economic evaluation that aims to assess whether a minimally invasive strategy is more efficient in allocating resources than the conventional strategy for managing restorations in primary teeth and extrapolating these findings to a longer time horizon. Methods A trial-based economic evaluation will be conducted, including three cost-effectiveness analyses (CEA) and one cost-utility analysis (CUA). These analyses will be based on the main trial (CARDEC-03/NCT03520309), in which children aged 3 to 10 were included and randomized to one of the diagnostic strategies (based on FDI or CARS). An examiner will assess children’s restorations using the randomized strategy, and treatment will be recommended according to the same criteria. The time horizon for this study is 2 years, and we will adopt the societal perspective. The average costs per child for 24 months will be calculated. Three different cost-effectiveness analyses (CEA) will be performed. For CEAs, the effects will be the number of operative interventions (primary CEA analysis), the time to these new interventions, the percentage of patients who did not need new interventions in the follow-up, and changes in children’s oral health-related quality of life (secondary analyses). For CUA, the effect will be tooth-related quality-adjusted life years (QALYs). Intention-to-treat analyses will be conducted. Finally, we will assess the difference when using the minimally invasive strategy for each health effect (∆effect) compared to the conventional strategy (based on FDI) as the reference strategy. The same will be calculated for related costs (∆cost). The discount rate of 5% will be applied for costs and effects. We will perform deterministic and probabilistic sensitivity analyses to handle uncertainties. The net benefit will be calculated, and acceptability curves plotted using different willingness-to-pay thresholds. Using Markov models, a longer-term economic evaluation will be carried out with trial results extrapolated over a primary tooth lifetime horizon. Discussion The main trial is ongoing, and data collection is still not finished. Therefore, economic evaluation has not commenced. We hypothesize that conventional strategy will be associated with more need for replacements of restorations in primary molars. These replacements may lead to more reinterventions, leading to higher costs after 2 years. The health effects will be a crucial aspect to take into account when deciding whether the minimally invasive strategy will be more efficient in allocating resources than the conventional strategy when considering the management of restorations in primary teeth. Finally, patients/parents preferences and consequent utility values may also influence this final conclusion about the economic aspects of implementing the minimally invasive approach for managing restorations in clinical practice. Therefore, these trial-based economic evaluations may bring actual evidence of the economic impact of such interventions. Trial registration NCT03520309. Registered May 9, 2018. Economic evaluations (the focus of this plan) are not initiated at the moment.

Cell-Free Biomimetic Mineralization Strategies to Regenerate the Enamel Microstructure

The distinct architecture of native enamel gives it its exquisite appearance and excellent intrinsic-extrinsic fracture toughening properties. However, damage to the enamel is irreversible. At present, the clinical treatment for enamel lesion is an invasive method; besides, its limitations, caused by the chemical and physical difference between restorative materials and dental hard tissue, makes the restorative effects far from ideal. With more investigations on the mechanism of amelogenesis, biomimetic mineralization techniques for enamel regeneration have been well developed, which hold great promise as a non-invasive strategy for enamel restoration. This review disclosed the chemical and physical mechanism of amelogenesis; meanwhile, it overviewed and summarized studies involving the regeneration of enamel microstructure in cell-free biomineralization approaches, which could bring new prospects for resolving the challenges in enamel regeneration.

The effect of early invasive strategy on mortality outcome in patients with chronic kidney disease presenting with non-ST segment elevation myocardial infarction

Background Current guidelines recommend an early invasive strategy for patients with non-ST segment elevation myocardial infarction (NSTEMI). Purpose To evaluate whether early invasive strategy is associated with better outcome among patients with chronic kidney disease (CKD). Methods Retrospective cohort analysis of consecutive patients with NSTEMI between 2008 and 2021. Glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation. Invasively treated patients were dichotomized into early (<24 hours) and non-early groups. Mortality data was available for all patients from a national registry. Multivariate Cox regression models with interaction analysis were applied. Results Final study population comprised 7,107 NSTEMI patients, of whom 3,172 (45%) had eGFR <60 ml/min/1.73m2. 1,988 (28%) and 973 (14%) patients had eGFR under 45 and 30 ml/min/1.73m2, respectively. 3,529 (50%) patients were treated invasively, among them 1837 (52%) underwent early invasive strategy. Patients in the early invasive group were younger (64 vs. 68 years, p<0.001) and were less likely to have comorbidities including kidney disease. During a median follow-up of 3 years (IQR 1.2–5.2), 2,552 (36%) patients died. Kaplan Meier survival analysis demonstrated that the cumulative probability of death was 50%, 15%, and 6% among patients in the conservative, non-early, and early invasive groups respectively (p Log-rank <0.001). Subgroup analysis of invasively managed patients showed that early invasive strategy was associated with a significant 32% reduced risk of death in a multivariate model (95% CI 0.56–0.82, p<0.001), but this associated benefit was modified by eGFR (p for interaction 0.045). The modification effect of CKD on the association of early invasive strategy with outcome was most pronounced among invasively treated patients with eGFR <45 ml/min/1.73m2, with no survival benefit for early invasive approach in these patients (HR 0.8, 95% CI 0.57–1.14, p=0.221 vs. HR 0.6 95% CI 0.45–0.72, p<0.001; p for interaction=0.046). Conclusion Among invasively treated NSTEMI patients, the benefit of early invasive strategy is modified by CKD, and limited to those with eGFR ≥45 ml/min/1.73m2. FUNDunding Acknowledgement Type of funding sources: None.