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EuroIntervention : Journal of EuroPCR... Jul 2023Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to... (Randomized Controlled Trial)
Randomized Controlled Trial
P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial.
Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).
Topics: Humans; Platelet Aggregation Inhibitors; Ticagrelor; Acute Coronary Syndrome; Prasugrel Hydrochloride; Percutaneous Coronary Intervention; Drug Therapy, Combination; Drug-Eluting Stents; Aspirin; Hemorrhage; Treatment Outcome
PubMed: 37306039
DOI: 10.4244/EIJ-D-23-00125 -
International Journal of Molecular... Aug 2023The incidence of prostate cancer (PC) has risen annually. PC mortality is explained by the metastatic disease (mPC). There is an intermediate scenario in which patients... (Review)
Review
The incidence of prostate cancer (PC) has risen annually. PC mortality is explained by the metastatic disease (mPC). There is an intermediate scenario in which patients have non-mPC but have initiated a metastatic cascade through epithelial-mesenchymal transition. There is indeed a need for more and better tools to predict which patients will progress in the future to non-localized clinical disease or already have micrometastatic disease and, therefore, will clinically progress after primary treatment. Biomarkers for the prediction of mPC are still under development; there are few studies and not much evidence of their usefulness. This review is focused on tissue-based genomic biomarkers (TBGB) for the prediction of metastatic disease. We develop four main research questions that we attempt to answer according to the current evidence. Why is it important to predict metastatic disease? Which tests are available to predict metastatic disease? What impact should there be on clinical guidelines and clinical practice in predicting metastatic disease? What are the current prostate cancer treatments? The importance of predicting metastasis is fundamental given that, once metastasis is diagnosed, quality of life (QoL) and survival drop dramatically. There is still a need and space for more cost-effective TBGB tests that predict mPC disease.
Topics: Male; Female; Humans; Quality of Life; Prostatic Neoplasms; Biomarkers; Genital Neoplasms, Female; Neoplasm Metastasis
PubMed: 37569883
DOI: 10.3390/ijms241512508 -
Neuroscience and Biobehavioral Reviews Mar 2024A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the... (Review)
Review
A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the association between physical activity and suicidal ideation, attempts, and deaths has not been systematically appraised in clinical samples. We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, EMBASE, and PsycINFO for observational studies investigating the influence of physical activity on suicidal behavior up to December 6, 2023. Of 116 eligible full-text studies, seven (n = 141691) were included. Depression was the most frequently studied mental condition (43%, k = 3), followed by chronic pain as the most common other medical condition (29%, k = 2). Two case-control studies examined suicide attempts and found an association between physical activity and a reduced frequency of such attempts. However, in studies examining suicidal ideation (k = 3) or suicide deaths (k = 2), no consistent associations with physical activity were observed. Overall, our systematic review found that physical activity may be linked to a lower frequency of suicide attempts in non-prospective studies involving individuals with mental disorders.
Topics: Humans; Suicide, Attempted; Suicidal Ideation; Risk Factors; Mental Disorders; Exercise
PubMed: 38246231
DOI: 10.1016/j.neubiorev.2024.105547 -
Ophthalmology Science 2024The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a...
PURPOSE
The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD.
DESIGN
Prospectively designed, cross-sectional study.
PARTICIPANTS
Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal.
METHODS
All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons.
MAIN OUTCOME MEASURES
Plasma metabolite levels associated with OCT features.
RESULTS
We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed.
CONCLUSIONS
To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found after the references.
PubMed: 37869026
DOI: 10.1016/j.xops.2023.100357 -
Aging Cell Apr 2024Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly...
Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear and penalized regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all-cause mortality. Seven-fold cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability.
PubMed: 38637937
DOI: 10.1111/acel.14164 -
Microorganisms Jan 2024(Linnaeus, 1758) (Hemiptera, Aphrophoridae) was recently classified as a pest due to its ability to act as a vector of the phytopathogen . This insect has been reported...
(Linnaeus, 1758) (Hemiptera, Aphrophoridae) was recently classified as a pest due to its ability to act as a vector of the phytopathogen . This insect has been reported to harbour several symbiotic bacteria that play essential roles in health and fitness. However, the factors driving bacterial assemblages remain largely unexplored. Here, the bacteriome associated with different organs (head, abdomen, and genitalia) of males and females of was characterized using culturally dependent and independent methods and compared in terms of diversity and composition. The bacteriome of is enriched in Proteobacteria, Bacteroidota, and Actinobacteria phyla, as well as in Sulcia and genera. The most frequent isolates were , , and sp.1. Males display a more diverse bacterial community than females, but no differences in diversity were found in distinct organs. However, the organ shapes the bacteriome structure more than sex, with the Microbacteriaceae family revealing a high level of organ specificity and the Blattabacteriaceae family showing a high level of sex specificity. Several symbiotic bacterial genera were identified in for the first time, including , , , , and . Differences in the bacterial composition within organs and sexes suggest an adaptation of bacteria to particular insect tissues, potentially shaped by their significance in the life and overall fitness of . Although more research on the bacteria of interactions is needed, such knowledge could help to develop specific bacterial-based insect management strategies.
PubMed: 38399702
DOI: 10.3390/microorganisms12020298 -
Journal of Global Antimicrobial... Sep 2023Emergence of carbapenemase and tigecycline resistance genes in pathogens threatens the efficacy of last-resort antibiotics. High attention should be paid to the spread...
OBJECTIVES
Emergence of carbapenemase and tigecycline resistance genes in pathogens threatens the efficacy of last-resort antibiotics. High attention should be paid to the spread and convergence of such resistance genes. This study reports an extensively drug-resistant (XDR) Providencia rettgeri clinical strain co-harbouring carbapenemase genes bla, bla and the tmexCD3-toprJ1b gene cluster.
METHODS
The phenotype and genotype of P. rettgeri Pre20-95 were investigated by antimicrobial susceptibility testing, conjugation assay, stability testing and whole genome sequencing. Bioinformatics tools were used to uncover the genetic structures of its multidrug-resistant (MDR) plasmid pPre20-95-1 and SXT/R391 integrative and conjugative element ICEPreChn20-95.
RESULTS
P. rettgeri strain Pre20-95 was isolated from a human clinical infection and displayed an extensively drug-resistant (XDR) phenotype. Whole genome sequencing (WGS) analysis identified a pPrY2001-like MDR plasmid, namely pPre20-95-1, co-harbouring bla and bla genes in Pre20-95. The multidrug resistance region of pPre20-95-1 was composed of a Tn6625-derived module and a ∆Tn1696 structure, and bla and bla were located in a composite Tn structure consisting of insertion sequences ISCR1 and ISAba125 and an In125-like class 1 integron, respectively. Furthermore, the novel RND efflux pump gene cluster tmexCD3-toprJ1b was identified on the SXT/R391 ICE ICEPreChn20-95 of its chromosome, and reverse PCR showed that it could form a circular intermediate for transmission.
CONCLUSION
Our findings highlight further dissemination of the tmexCD3-toprJ1b gene cluster into a clinical isolate of P. rettgeri and convergence with multiple carbapenemase genes, which increases the risk of the emergence of XDR strains and threatens the treatment of Enterobacterales bacterial infections.
Topics: Humans; Enterobacteriaceae Infections
PubMed: 37536658
DOI: 10.1016/j.jgar.2023.07.018 -
Molecular Phylogenetics and Evolution Jun 2024The tribe Astereae (Asteraceae) includes 36 subtribes and 252 genera, and is distributed worldwide in temperate and tropical regions. One of the subtribes, Celmisiinae...
The tribe Astereae (Asteraceae) includes 36 subtribes and 252 genera, and is distributed worldwide in temperate and tropical regions. One of the subtribes, Celmisiinae Saldivia, has been recently circumscribed to include six genera and ca. 160 species, and is restricted to eastern Australia, New Zealand, and New Guinea. The species show an impressive range of growth habit, from small herbs and ericoid subshrubs to medium-sized trees. They live in a wide range of habitats and are often dominant in subalpine and alpine vegetation. Despite the well-supported circumscription of Celmisiinae, uncertainties have remained about their internal relationships and classification at genus and species levels. This study exploited recent advances in high-throughput sequencing to build a robust multi-gene phylogeny for the subtribe Celmisiinae. The target enrichment Angiosperms353 bait set and the hybpiper-nf and paragone-nf pipelines were used to retrieve, infer, and assemble orthologous loci from 75 taxa representing all the main putative clades within the subtribe. Because of the diploidised ploidy level in Celmisiinae, as well as missing data in the assemblies, uncertainty remains surrounding the inference of orthology detection. However, based on a variety of gene-family sets, coalescent and concatenation-based phylogenetic reconstructions recovered similar topologies. Paralogy and missing data in the gene-families caused some problems, but the estimated phylogenies were well-supported and well-resolved. The phylogenomic evidence supported Celmisiinae and three main clades: the Pleurophyllum clade (Pleurophyllum, Macrolearia and Damnamenia), mostly in the New Zealand Subantarctic Islands, Celmisia of mainland New Zealand and Australia, and Shawia (including 'Olearia pro parte' and Pachystegia) of New Zealand, Australia and New Guinea. The results presented here add to the accumulating support for the Angiosperms353 bait set as an efficient method for documenting plant diversity.
Topics: Humans; Phylogeny; Asteraceae; Biological Evolution; Australia; High-Throughput Nucleotide Sequencing
PubMed: 38508479
DOI: 10.1016/j.ympev.2024.108064 -
Frontiers in Cardiovascular Medicine 2023Atrial fibrillation (AF) confers a major healthcare burden from hospitalisations and AF-related complications, such as stroke and heart failure. We performed an...
BACKGROUND
Atrial fibrillation (AF) confers a major healthcare burden from hospitalisations and AF-related complications, such as stroke and heart failure. We performed an electronic health records-wide association study to identify the most frequent reasons for healthcare utilization, pre and post new-onset AF.
METHODS
Prospective cohort study with the linked electronic health records of 5.6 million patients in the United Kingdom Clinical Practice Research Datalink (1998-2016). A cohort study with AF patients and their age-and sex matched controls was implemented to compare the top 100 reasons of frequent hospitalisation and primary consultation.
RESULTS
Of the 199,433 patients who developed AF, we found the most frequent healthcare interactions to be cardiac, cerebrovascular and peripheral-vascular conditions, both prior to AF diagnosis (41/100 conditions in secondary care, such as cerebral infarction and valve diseases; and 33/100 conditions in primary care), and subsequently (47/100 conditions hospital care and 48 conditions in primary care). There was a high representation of repeated visits for cancer and infection affecting multiple organ systems. We identified 10 novel conditions which have not yet been associated with AF: folic acid deficiency, pancytopenia, idiopathic thrombocytopenic purpura, seborrheic dermatitis, lymphoedema, angioedema, laryngopharyngeal reflux, rib fracture, haemorrhagic gastritis, inflammatory polyneuropathies.
CONCLUSION
Our nationwide data provide knowledge and better understanding of the clinical needs of AF patients suggesting: (i) groups at higher risk of AF, where screening may be more cost-effective, and (ii) potential complications developing following new-onset AF that can be prevented through implementation of comprehensive integrated care management and more personalised, tailored treatment.
CLINICAL TRIAL REGISTRATION
NCT04786366.
PubMed: 37840952
DOI: 10.3389/fcvm.2023.1204892 -
BMC Pediatrics Oct 2023Parental complaints about feeding difficulties (FD) during childhood are frequent in pediatrics. Behavioral factors about children's feeding and parental aspects are...
BACKGROUND
Parental complaints about feeding difficulties (FD) during childhood are frequent in pediatrics. Behavioral factors about children's feeding and parental aspects are fundamental in solving these problems, but research in this area lacks information considering the joint presence of fathers and mothers. Thus, this study aimed to investigate the features of children, parents and mealtime practices related to FD reported by fathers and mothers and to identify parenting styles, mealtime actions, practices and factors associated with FD in children.
METHODS
323 parents (226 mothers and 97 fathers) of children aged 1 to 7 years were recruited in the emergency waiting room at Sabará Hospital Infantil, in São Paulo, Brazil, and self-completed electronic questionnaires on parenting style (Caregiver's Feeding Styles Questionnaire), parents' mealtime actions (Parent Mealtime Action Scale), socioeconomic information, personal and children's health data and routine meal practices.
RESULTS
The prevalence of FD in children was 26.6%. Indulgent parenting style was the most frequent (44.2%), followed by authoritarian (25.1%), authoritative (23.8%), and uninvolved (6.9%) styles. Most parents (75.8%) reported presence during meals, and 83.6% used distractions. Regression analyses after adjustments showed, as factors associated with FD, female children (OR: 2.06; 95%CI: 1.19-3.58), parents' FD history (OR: 3.16; 95%CI: 1.77-5.64), and greater frequency of parents' behavior of offering many food options (OR: 2.69; 95%CI: 1.18-6.14). Parents with indulgent styles had decreased chances of reporting FD in their children (OR: 0.13; 95%CI: 0.06-0.27). Furthermore, the practice of children sharing the family menu (OR: 0.43; 95%CI: 0.18-0.99) and higher frequency of parents' behavior of setting snack limits (OR: 0.44; 95%CI: 0.23-0.85) were inversely associated with FD.
CONCLUSIONS
This study reinforces the multifactorial aspects involved in the feeding difficulties context. It points out the importance of expanding knowledge of the individual role of fathers and mothers to compose a scenario that can guide future studies and interventions.
TRIAL REGISTRATION
CAAE #99221318.1.0000.5567 with registration number 2,961,598.
Topics: Child; Humans; Female; Feeding Behavior; Brazil; Parents; Mothers; Parenting; Parent-Child Relations; Surveys and Questionnaires
PubMed: 37898797
DOI: 10.1186/s12887-023-04369-4