BACKGROUND: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination. METHODS: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe. In stage 1, healthy MenACWY vaccine-naive or -experienced 10- to 25-year-olds were randomized 1:2 to receive MenABCWY and placebo or MenB-fHbp and MenACWY-CRM. Eligible participants were randomly selected to participate in stage 2, which was an open-label immunopersistence and booster extension. Immunogenicity was assessed through serum bactericidal antibody using human complement (hSBA) assays with serogroups A/C/W/Y (MenA/C/W/Y) and 4 primary serogroup B (MenB) test strains. Immunogenicity endpoints included hSBA seroprotection rates through 48 months after primary vaccination and 1 month after the booster. Safety endpoints included booster reactogenicity events and adverse events (AEs). RESULTS: Of 1379 eligible participants, 353 entered stage 2; 242 completed the 48-month blood draw after primary vaccination and 240 completed the booster vaccination phase. MenA/C/W/Y seroprotection rates remained high for 4 years following a 2-dose MenABCWY primary series (MenACWY-naive, 62.0 %-100.0 %; MenACWY-experienced, 98.7 %-100.0 %) and trended higher than those after a single MenACWY-CRM dose (MenACWY-naive, 38.1 %-95.2 %; MenACWY-experienced, 89.7 %-100.0 %). Corresponding seroprotection rates against MenB remained stable and generally higher than baseline (MenABCWY, 18.2 %-36.6 %; MenB-fHbp, 16.2 %-31.9 % across strains). Following a booster, seroprotection rates against all 5 serogroups were ≥ 93.8 % across groups. Most booster dose reactogenicity events were mild or moderate in severity, and AEs were infrequent. CONCLUSIONS: Immune responses remained high for MenA/C/W/Y and above baseline for MenB through 4 years after the MenABCWY primary series, with robust responses for all 5 serogroups observed following a booster. The MenABCWY booster had an acceptable safety and tolerability profile consistent with the primary series. NCT03135834.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunogenicita vakcíny MeSH
• komplement imunologie   MeSH
• lidé MeSH
• meningokokové infekce * prevence a kontrola   imunologie   MeSH
• meningokokové vakcíny * imunologie   škodlivé účinky   aplikace a dávkování   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Neisseria meningitidis imunologie   MeSH
• protilátky bakteriální * krev   MeSH
• sekundární imunizace * metody   MeSH
• séroskupina MeSH
• vakcíny konjugované imunologie   aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

In recent years, several international urological societies have published guidelines on the diagnosis, treatment, and follow-up of urethral strictures, but a guideline for the German-speaking region has not been available to date. This summary provides a detailed comparison of the guidelines of the European Association of Urology (EAU), American Urological Association (AUA) and the Société Internationale d'Urologie (SIU) with regard to the treatment of anterior urethral strictures, i.e. from the bulbar urethra to the meatus. In the following work, differences and specific recommendations in the guidelines are highlighted. In particular, the three guidelines largely agree with regard to diagnostic workup and follow-up. However, divergences exist in the management of anterior urethral strictures, particularly with regard to the use of endoscopic therapeutic approaches and the use of urethral stents. In addition, the EAU provides more comprehensive and detailed recommendations on urethroplasty techniques and specific patient follow-up. The EAU guidelines are the most current and were the first to include instructions for urethral strictures in women and individuals with gender incongruence after genital approximation surgery. Reconstructive urology is a rapidly evolving specialty and, thus, the clinical approach has been changing accordingly. Although guideline recommendations have become more inclusive and comprehensive, more high-quality data are needed to further improve the level of evidence.

• MeSH
• lidé MeSH
• správnost dat MeSH
• striktura uretry * diagnóza   MeSH
• uretra chirurgie   MeSH
• urologie * MeSH
• zákroky plastické chirurgie * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Spojené státy americké MeSH

In light of recently published international guidelines concerning the diagnosis, treatment, and aftercare of urethral strictures and stenoses, the objective of this study was to synthesize an overview of guideline recommendations provided by the American Urological Association (AUA, 2023), the Société Internationale d'Urologie (SIU, 2010), and the European Association of Urology (EAU, 2023). The recommendations offered by these three associations, as well as the guidelines addressing urethral trauma from the EAU, AUA, and the Urological Society of India (USI), were assessed in terms of their guidance on posterior urethral stenosis. On the whole, the recommendations from the various guidelines exhibit considerable alignment. However, SIU and EAU place a stronger emphasis on the role of repeated endoscopic treatment compared to AUA. The preferred approach for managing radiation-induced bulbomembranous stenosis remains a subject of debate. Furthermore, endoscopic treatments enhanced with intralesional therapies may potentially serve as a significant treatment modality for addressing even fully obliterated stenoses.

• MeSH
• endoskopie MeSH
• lidé MeSH
• stenóza diagnóza   MeSH
• striktura uretry * diagnóza   MeSH
• uretra zranění   MeSH
• urologie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Spojené státy americké MeSH

BACKGROUND: Subtle, prognostically important ECG features may not be apparent to physicians. In the course of supervised machine learning, thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. We aimed to investigate whether neural network-derived ECG features could be used to predict future cardiovascular disease and mortality and have phenotypic and genotypic associations. METHODS: We extracted 5120 neural network-derived ECG features from an artificial intelligence-enabled ECG model trained for 6 simple diagnoses and applied unsupervised machine learning to identify 3 phenogroups. Using the identified phenogroups, we externally validated our findings in 5 diverse cohorts from the United States, Brazil, and the United Kingdom. Data were collected between 2000 and 2023. RESULTS: In total, 1 808 584 patients were included in this study. In the derivation cohort, the 3 phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared with phenogroup A (hazard ratio, 1.20 [95% CI, 1.17-1.23]; P<0.0001; phenogroup A mortality, 2.2%; phenogroup B mortality, 6.1%). In univariate analyses, we found phenogroup B had a significantly greater risk of mortality in all cohorts (log-rank P<0.01 in all 5 cohorts). Phenome-wide association study showed phenogroup B had a higher rate of future atrial fibrillation (odds ratio, 2.89; P<0.00001), ventricular tachycardia (odds ratio, 2.00; P<0.00001), ischemic heart disease (odds ratio, 1.44; P<0.00001), and cardiomyopathy (odds ratio, 2.04; P<0.00001). A single-trait genome-wide association study yielded 4 loci. SCN10A, SCN5A, and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target. CONCLUSIONS: Neural network-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.

• MeSH
• časové faktory MeSH
• elektrokardiografie * MeSH
• fenotyp * MeSH
• hodnocení rizik MeSH
• kardiovaskulární nemoci diagnóza   mortalita   genetika   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuronové sítě (počítačové) * MeSH
• prediktivní hodnota testů * MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční frekvence MeSH
• strojové učení bez učitele MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Spojené státy americké MeSH

BACKGROUND: Ethno-racial disparities in cardiometabolic diseases are driven by socioeconomic, behavioral, and environmental factors. Bayesian networks offer an approach to analyze the complex interaction of the multi-tiered modifiable factors and non-modifiable demographics that influence the incidence and progression of cardiometabolic disease. METHODS: In this study, we learn the structure and parameters of a Bayesian network based on 20 years of data from the US National Health and Nutrition Examination Survey to explore the pathways mediating associations between ethno-racial group and cardiometabolic outcomes. The impact of different factors on cardiometabolic outcomes by ethno-racial group is analyzed using conditional probability queries. RESULTS: Multiple pathways mediate the indirect association from ethno-racial group to cardiometabolic outcomes: (1) ethno-racial group to education and to behavioral factors (diet); (2) education to behavioral factors (smoking, physical activity, and-via income-to alcohol); (3) and behavioral factors to adiposity-based chronic disease (ABCD) and then other cardiometabolic drivers. Improved diet and physical activity are associated with a larger decrease in probability of ABCD stage 4 among non-Hispanic White (NHW) individuals compared to non-Hispanic Black (NHB) and Hispanic (HI) individuals. CONCLUSION: Education, income, and behavioral factors mediate ethno-racial disparities in cardiometabolic outcomes, but traditional behavioral factors (diet and physical activity) are less influential among NHB or HI individuals compared to NHW individuals. This suggests the greater contribution of unmeasured individual- and/or neighborhood-level structural determinants of health that impact cardiometabolic drivers among NHB and HI individuals. Further study is needed to discover the nature of these unmeasured determinants to guide cardiometabolic care in diverse populations.

• MeSH
• Bayesova věta * MeSH
• běloch MeSH
• černoši nebo Afroameričané MeSH
• chronická nemoc MeSH
• disparity zdravotního stavu * MeSH
• dospělí MeSH
• etnicita MeSH
• Hispánci a Latinoameričané MeSH
• kardiovaskulární nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• rasové skupiny MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• výživa - přehledy * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Spojené státy americké MeSH

BACKGROUND: Medication non-adherence is a common issue in chronic illness. The World Health Organization has recognized a need for a valid and reliable method of measuring adherence to understand and mitigate non-adherence. This study aimed to psychometrically evaluate the English version of the Adelphi Adherence Questionnaire (ADAQ©), a questionnaire designed to assess patient-reported medication adherence across multiple therapy areas, in patients with Osteoarthritis (OA). METHODOLOGY: Data from the Adelphi OA Disease Specific ProgrammeTM, a survey of physicians and their consulting adult patients with OA conducted in the United States, November 2020 to March 2021, was used to assess the psychometric properties of the ADAQ. Patients completed the ADAQ, Adherence to Refills and Medication Scale (ARMS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EQ-5D-3L. The measurement model of the 13-item ADAQ was assessed and refined using latent variable modelling (Multiple Indicator Multiple Cause, confirmatory and exploratory factor analyses, item response theory, Mokken scaling, and bifactor analyses). Correlational analyses (Spearman's rank and polyserial as appropriate) with ARMS, WOMAC, and EQ-5D-3L scores assessed construct validity. Anchor- and distribution-based analyses were performed to estimate between-group clinically important differences (CID). RESULTS: Overall, 723 patients were included in this analysis (54.5% female, 69.0% aged ≥ 60). Latent variable modelling indicated a unidimensional reflective model was appropriate, with a bifactor model confirming an 11-item essentially unidimensional score. Items 12 and 13 were excluded from scoring as they measured a different concept. The ADAQ had high internal reliability with omega hierarchical and Cronbach's alpha coefficients of 0.89 and 0.97, respectively. Convergent validity was supported by moderate correlations with items of the ARMS, and physician-reported adherence and compliance. Mean differences in ADAQ score between high and low adherence groups yielded CID estimates between 0.49 and 1.05 points, with a correlation-weighted average of 0.81 points. CONCLUSION: This scoring model showed strong construct validity and internal consistency reliability when assessing medication adherence in OA. Future work should focus on confirming validity across a range of disease areas.

• MeSH
• adherence k farmakoterapii * psychologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoartróza * farmakoterapie   psychologie   MeSH
• průzkumy a dotazníky MeSH
• psychometrie * metody   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Spojené státy americké MeSH

Fibroblast activation protein (FAP) has been extensively studied as a cancer biomarker for decades. Recently, small-molecule FAP inhibitors have been widely adopted as a targeting moiety of experimental theranostic radiotracers. Here we present a fast qPCR-based analytical method allowing FAP inhibition screening in a high-throughput regime. To identify clinically relevant compounds that might interfere with FAP-targeted approaches, we focused on a library of FDA-approved drugs. Using the DNA-linked Inhibitor Antibody Assay (DIANA), we tested a library of 2667 compounds within just a few hours and identified numerous FDA-approved drugs as novel FAP inhibitors. Among these, prodrugs of cephalosporin antibiotics and reverse transcriptase inhibitors, along with one elastase inhibitor, were the most potent FAP inhibitors in our dataset. In addition, by employing FAP DIANA in the quantification mode, we were able to determine FAP concentrations in human plasma samples. Together, our work expands the repertoire of FAP inhibitors, analyzes the potential interference of co-administered drugs with FAP-targeting strategies, and presents a sensitive and low-consumption ELISA alternative for FAP quantification with a detection limit of 50 pg/ml.

• MeSH
• cefalosporiny chemie   farmakologie   MeSH
• endopeptidasy * metabolismus   MeSH
• knihovny malých molekul farmakologie   chemie   MeSH
• lidé MeSH
• membránové proteiny * antagonisté a inhibitory   metabolismus   MeSH
• molekulární struktura MeSH
• rychlé screeningové testy * MeSH
• schvalování léčiv MeSH
• serinové endopeptidasy * metabolismus   MeSH
• Úřad Spojených států pro potraviny a léky MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• želatinasy * antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Spojené státy americké MeSH

• MeSH
• kurzy a stáže v nemocnici MeSH
• lidé MeSH
• neurologie MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Spojené státy americké MeSH

BACKGROUND: Reduction mammoplasty is popular among people of various age groups, yet the impact of age on postoperative outcomes remains debated. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (2008-2021) was queried to identify adult female patients who underwent reduction mammoplasty. Patients were categorized into 10-year age brackets (i.e., 18-29, 30-39, 40-49, 50-59, 60-69, and >70 years). We compared age-dependent 30-day outcomes via confounder-adjusted multivariate analyses. RESULTS: 40,958 female patients (mean age: 41 ± 14 years and mean body mass index: 31 ± 6.1 kg/m2) were identified. Complications occurred in 6.4% (n = 2635) of cases, with 770 (1.9%) and 483 (1.2%) patients requiring reoperation and readmission, respectively. 1706 (4.2%) women experienced surgical complications, whereas medical complications were generally rare (n = 289; 0.7%). Compared with women aged 18-29 years, risks of any, surgical, and medical complications were higher for patients aged 30-39 years (OR: 1.22, p < 0.01; OR: 1.05, p = 0.51; OR: 1.84, p < 0.01), 40-49 years (OR: 1.34, p < 0.01; OR: 1.17, p = 0.04; OR: 1.54, p = 0.03), 50-59 years (OR: 1.45, p < 0.01; OR: 1.31, p < 0.01; OR: 1.78, p < 0.01), 60-69 years (OR: 1.38 years, p < 0.01; OR: 1.29, p = 0.01; OR: 1.71, p < 0.01), and >70 years (OR: 1.25, p = 0.18; OR: 1.01, p = 0.98; OR: 1.86, p = 0.14). Patients aged >30 years were also more likely to require readmissions and reoperations. CONCLUSION: Patient age significantly affects outcomes after reduction mammoplasty, with the lowest risk in patients aged <30 years. Importantly, the association between age and postoperative morbidity was not linear. These findings can help guide informed decisions, recognizing that while age is a factor, it is not the sole determinant of risk.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mamoplastika * metody   statistika a číselné údaje   škodlivé účinky   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pooperační komplikace * epidemiologie   MeSH
• reoperace * statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• věkové faktory MeSH
• výsledek terapie MeSH
• znovupřijetí pacienta statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Spojené státy americké MeSH

• MeSH
• dějiny 19. století MeSH
• dějiny 20. století MeSH
• injekce intravenózní dějiny   MeSH
• jedy dějiny   toxicita   MeSH
• lékaři dějiny   MeSH
• lidé MeSH
• trest smrti * dějiny   metody   MeSH
• vynálezy dějiny   MeSH
• významné osobnosti MeSH
• Check Tag
• dějiny 19. století MeSH
• dějiny 20. století MeSH
• lidé MeSH
• Geografické názvy
• Česká republika MeSH
• Spojené státy americké MeSH