Summary Background Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting ...bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. Findings The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction =0·007), and exerted a significant ischaemic benefit only in this latter group. Interpretation The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. Funding None.
A
bstract
We consider an extension of the Standard Model that accounts for the muon
g −
2 tension and neutrino masses and study in detail dark matter phenomenology. The model under consideration ...includes a WIMP and a FIMP scalar dark matter candidates and thus gives rise to two-component dark matter scenarios. We discuss different regimes and mechanisms of production, including the novel freeze-in semi-production, and show that the WIMP and FIMP together compose the observed relic density today. The presence of the extra scalar fields allows phase transitions of the first order. We examine the evolution of the vacuum state and discuss stochastic gravitational wave signals associated with the first-order phase transition. We show that the gravitational wave signals may be probed by future gravitational wave experiments which may serve as a complementary detection signal.
Ritual as metaphor Della Costa, Francesco
Anthropological theory,
03/2023, Letnik:
23, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The effectiveness of ritual is a major anthropological question. In this paper, I challenge some of the explanations anthropologists have provided to such a question and I attempt to formulate an ...original theorization of ritual as metaphor. The proposed hypothesis is grounded in two inspiring concepts: Ernesto De Martino's idea of “dehistorification” as the main technique of the ritual and Bruce Kapferer's “virtuality” as its proper dynamic dimension. Drawing on these theoretical foundations and a direct ethnographic experience and conceiving of ritual as a practice rather than as a symbol, I propose to regard it as a particular practice of metaphorization that is not representative of reality but effective on it.
A
bstract
We consider an extension of the Standard Model that explains the neutrino masses and has a rich dark matter phenomenology. The model has two dark matter candidates, a vector WIMP and a ...fermion FIMP, and the sum of their relic densities matches the total dark matter abundance. We extensively study the dark matter production mechanisms and its connection with the neutrino sector, together with various bounds from present and future experiments. The extra scalar field in the model may induce a first-order phase transition in the early Universe. We study the production of stochastic gravitational waves associated with the first-order phase transition. We show that the phase transition can be strong, and thus the model may satisfy one of the necessary conditions for a successful electroweak baryogenesis. Detectability of the phase transition-associated gravitational waves is also discussed.
This study systematically reviews costing studies of seasonal influenza-like illness (ILI) in high-income countries. Existing reviews on the economic impact of ILI do not report information on drug ...consumption and its costs, nor do they provide data on the overall cost per episode.
The PRISMA-P checklist was used to design the research protocol. Studies included were cost of illness analysis (COI) and modeling studies that estimated the cost of ILI episodes. Records were searched from January 2000 to December 2016 in electronic bibliographic databases including Medline, Embase, Science Direct, the Cochrane Library, the Centre for Reviews and Disseminations of the University of York, and Google scholar. References from the included studies were hand-searched for completion. Abstract screening, full-text analysis and data extraction were performed by two reviewers independently and discrepancies were resolved by discussion with a third reviewer. A standardized, pre-piloted form was used for data extraction. All costs were converted to 2015 US$ Purchasing Power Parities.
The literature search identified 5,104 records. After abstract and title screening, 76 studies were analyzed full-text and 27 studies were finally included in the review. Full estimates of the cost per episode range from US$19 in Korea to US$323 in Germany. Particularly, the cost per episode of laboratory confirmed influenza cases was estimated between US$64 and US$73. Inpatient and outpatient services account for the majority of the costs. Differences in the estimates may reflect country-specific characteristics, as well as other study-specific features including study design, identification strategy of ILI cases, study populations and types of costs included in the analysis. Children usually register higher costs, whereas evidence for the elderly is less conclusive. Patients risk-profile, co-morbidities and complications are the other important cost-drivers. None of the papers considered appropriateness in resource use (e.g. abuse of antibiotics). Despite cost of illness studies have ultimately a descriptive role, evidence on (in)appropriateness is useful for policy-makers.
Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and ...different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn's disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.
Obstructive sleep apnea (OSA) is a risk factor for several diseases and is correlated with other non-medical consequences that increase the disease's clinical and economic burden. However, OSA's ...impact is highly underestimated, also due to substantial diagnosis gaps.
This study aims at assessing the economic burden of OSA in the adult population in Italy by performing a cost-of-illness analysis with a societal perspective. In particular, we aimed at estimating the magnitude of the burden caused by conditions for which OSA is a proven risk factor.
A systematic literature review on systematic reviews and meta-analyses, integrated by expert opinion, was performed to identify all clinical and non-clinical conditions significantly influenced by OSA. Using the Population Attributable Fraction methodology, a portion of their prevalence and costs was attributed to OSA. The total economic burden of OSA for the society was estimated by summing the costs of each condition influenced by the disease, the costs due to OSA's diagnosis and treatment and the economic value of quality of life lost due to OSA's undertreatment.
Twenty-six clinical (e.g., diabetes) and non-clinical (e.g., car accidents) conditions were found to be significantly influenced by OSA, contributing to an economic burden ranging from €10.7 to €32.0 billion/year in Italy. The cost of impaired quality of life due to OSA undertreatment is between €2.8 and €9.0 billion/year. These costs are substantially higher than those currently borne to diagnose and treat OSA (€234 million/year).
This study demonstrates that the economic burden due to OSA is substantial, also due to low diagnosis and treatment rates. Providing reliable estimates of the economic impact of OSA at a societal level may increase awareness of the disease burden and help to guide evidence-based policies and prioritisation for healthcare, ultimately ensuring appropriate diagnostic and therapeutic pathways for patients.
Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk ...(HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized.
This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting.
Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.
Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity.
Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.
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Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial ...infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS.
In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding occurring >30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P < 0.001 and BARC 3a bleeding (RR 2.23; 95% CI 1.36-3.64; P = 0.001), and a risk similar to BARC 3b bleeding (RR 1.37; 95% CI 0.81-2.30; P = 0.242). Risk of death after MI was significantly lower than after BARC 3c bleeding (RR 0.22; 95% CI 0.13-0.36; P < 0.001). MI and bleeding had similar time-associations with mortality, which remained significant for several months, still being higher early after the event.
In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding.
Purpose
We present an automated method for extracting anatomical parameters from biplanar radiographs of the spine, which is able to deal with a wide scenario of conditions, including sagittal and ...coronal deformities, degenerative phenomena as well as images acquired with different fields of view.
Methods
The location of 78 landmarks (end plate centers, hip joint centers, and margins of the S1 end plate) was extracted from three-dimensional reconstructions of 493 spines of patients suffering from various disorders, including adolescent idiopathic scoliosis, adult deformities, and spinal stenosis. A fully convolutional neural network featuring an additional differentiable spatial to numerical (DSNT) layer was trained to predict the location of each landmark. The values of some parameters (T4–T12 kyphosis, L1–L5 lordosis, Cobb angle of scoliosis, pelvic incidence, sacral slope, and pelvic tilt) were then calculated based on the landmarks’ locations. A quantitative comparison between the predicted parameters and the ground truth was performed on a set of 50 patients.
Results
The spine shape predicted by the models was perceptually convincing in all cases. All predicted parameters were strongly correlated with the ground truth. However, the standard errors of the estimated parameters ranged from 2.7° (for the pelvic tilt) to 11.5° (for the L1–L5 lordosis).
Conclusions
The proposed method is able to automatically determine the spine shape in biplanar radiographs and calculate anatomical and posture parameters in a wide scenario of clinical conditions with a very good visual performance, despite limitations highlighted by the statistical analysis of the results.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material.
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