Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort (n = 1,162 total, n = 422 females) suggested that niacin metabolism was associated with incident major adverse cardiovascular events (MACE). Serum levels of the terminal metabolites of excess niacin, N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3-carboxamide (4PY), were associated with increased 3-year MACE risk in two validation cohorts (US n = 2,331 total, n = 774 females; European n = 832 total, n = 249 females) (adjusted hazard ratio (HR) (95% confidence interval) for 2PY: 1.64 (1.10-2.42) and 2.02 (1.29-3.18), respectively; for 4PY: 1.89 (1.26-2.84) and 1.99 (1.26-3.14), respectively). Phenome-wide association analysis of the genetic variant rs10496731, which was significantly associated with both 2PY and 4PY levels, revealed an association of this variant with levels of soluble vascular adhesion molecule 1 (sVCAM-1). Further meta-analysis confirmed association of rs10496731 with sVCAM-1 (n = 106,000 total, n = 53,075 females, P = 3.6 × 10-18). Moreover, sVCAM-1 levels were significantly correlated with both 2PY and 4PY in a validation cohort (n = 974 total, n = 333 females) (2PY: rho = 0.13, P = 7.7 × 10-5; 4PY: rho = 0.18, P = 1.1 × 10-8). Lastly, treatment with physiological levels of 4PY, but not its structural isomer 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice. Collectively, these results indicate that the terminal breakdown products of excess niacin, 2PY and 4PY, are both associated with residual CVD risk. They also suggest an inflammation-dependent mechanism underlying the clinical association between 4PY and MACE.
BACKGROUND: Heart failure is a common complication after myocardial infarction (MI) and is associated with increased mortality. Whether remote heart failure symptoms assessment after MI can improve risk stratification is unknown. The authors evaluated the association of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) with all-cause mortality after MI. METHODS AND RESULTS: Prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart center between June 2017 and September 2022 were used. Patients remotely completed the KCCQ 1 month after discharge. A total of 1135 (aged 64±12 years, 26.7% women) of 1721 eligible patients completed the KCCQ. Ranges of KCCQ scores revealed that 30 (2.6%), 114 (10.0%), 274 (24.1%), and 717 (63.2%) had scores <25, 25 to 49, 50 to 74, and ≥75, respectively. During a mean follow-up of 46 months (interquartile range, 29-61), 146 (12.9%) died. In a fully adjusted analysis, KCCQ scores <50 were independently associated with mortality (hazard ratio [HR], 6.05 for KCCQ <25, HR, 2.66 for KCCQ 25-49 versus KCCQ ≥50; both P<0.001). Adding the 30-day KCCQ to clinical risk factors improved risk stratification: change in area under the curve of 2.6 (95% CI, 0.3-5.0), Brier score of -0.6 (95% CI, -1.0 to -0.2), and net reclassification improvement of 0.71 (95% CI, 0.45-1.04). KCCQ items most strongly associated with mortality were walking impairment, leg swelling, and change in symptoms. CONCLUSIONS: Remote evaluation of heart failure symptoms using the KCCQ among patients recently discharged for MI identifies patients at risk for mortality. Whether closer follow-up and targeted therapy can reduce mortality in high-risk patients warrants further study.
- MeSH
- hospitalizace MeSH
- infarkt myokardu * komplikace diagnóza MeSH
- kvalita života MeSH
- lidé MeSH
- proporcionální rizikové modely MeSH
- propuštění pacienta MeSH
- srdeční selhání * terapie MeSH
- zdravotní stav MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2- ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. METHODS: Postmenopausal patients with HR+/HER2- ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). RESULTS: At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50-0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. CONCLUSIONS: This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2- ABC.
BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with cardiogenic shock despite the lack of evidence from adequately powered randomised clinical trials. Three trials reported so far were underpowered to detect a survival benefit; we therefore conducted an individual patient-based meta-analysis to assess the effect of VA-ECMO on 30-day death rate. METHODS: Randomised clinical trials comparing early routine use of VA-ECMO versus optimal medical therapy alone in patients presenting with infarct-related cardiogenic shock were identified by searching MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and trial registries until June 12, 2023. Trials were included if at least all-cause death rate 30 days after in-hospital randomisation was reported and trial investigators agreed to collaborate (ie, providing individual patient data). Odds ratios (ORs) as primary outcome measure were pooled using logistic regression models. This study is registered with PROSPERO (CRD42023431258). FINDINGS: Four trials (n=567 patients; 284 VA-ECMO, 283 control) were identified and included. Overall, there was no significant reduction of 30-day death rate with the early use of VA-ECMO (OR 0·93; 95% CI 0·66-1·29). Complication rates were higher with VA-ECMO for major bleeding (OR 2·44; 95% CI 1·55-3·84) and peripheral ischaemic vascular complications (OR 3·53; 95% CI 1·70-7·34). Prespecified subgroup analyses were consistent and did not show any benefit for VA-ECMO (pinteraction ≥0·079). INTERPRETATION: VA-ECMO did not reduce 30-day death rate compared with medical therapy alone in patients with infarct-related cardiogenic shock, and an increase in major bleeding and vascular complications was observed. A careful review of the indication for VA-ECMO in this setting is warranted. FUNDING: Foundation Institut für Herzinfarktforschung.
- MeSH
- intraaortální balónková pumpa MeSH
- kardiogenní šok * etiologie terapie MeSH
- krvácení etiologie MeSH
- lidé MeSH
- logistické modely MeSH
- mimotělní membránová oxygenace * škodlivé účinky MeSH
- randomizované kontrolované studie jako téma MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
BACKGROUND: Foot morphology is associated with altered loading of the ankle-foot complex in adolescent footballers, predisposing to pain and injury. However, usual singular plane clinical assessments do not accurately capture the 3D nature of foot morphology. A new approach is 3D laser scanning, with statistical shape model techniques creating individual-to-group comparison. However, no research exists on the adolescent, football-playing foot. Furthermore, a link between 3D foot morphology, and usual clinical and performance measures would be beneficial for practical implementation. METHODS: Four hundred forty-seven 3D foot scans from 224 elite male footballers (U12-U19) in bilateral stance were collected and further processed with statistical shape model techniques. Weighted shape parameters for individual principal components (Modes) were extracted for each foot. Centre of pressure displacement expressed as total travelled way in millimetres was calculated for bilateral and unilateral postural stability measures. Clinical assessments (Clarke's Angle, Resting Calcaneal Stance Position) were calculated on the 3D foot scans. Differences in weighted shape parameters, postural stability measures, and clinical assessments between age groups were determined by ANOVA. Correlations determined the relationship of Modes and clinical assessments to postural stability measures. Linear regression established if clinical assessments predicted the mode describing foot arch variation. RESULTS: Age groups significantly differed for Mode 1 (foot length), Mode 2 (foot arch), and Mode 5 (tibial rotation relative to the foot) (p < 0.05). Resting Calcaneal Stance Position (r = .663) and Clarke's Angle (r = -.445) were low-to-moderately correlated to Mode 2 (both p < 0.001), and linear regression found they were both significant predictors of Mode 2, though only moderately (R2 = .522). There were low correlations of foot morphology to the postural stability tests. CONCLUSION: This is the first study to describe the 3D foot morphology of male football-playing adolescents, and discover the differences between age groups. This will improve understanding and assessment of foot morphology in male adolescents because 2D techniques, as discovered in this study, do not strongly correlate to, nor predict, the 3D foot arch. Foot morphology was only lowly correlated to postural stability, thus a multifaceted program would be required for improvements.
- MeSH
- dolní končetina * MeSH
- hlezenní kloub MeSH
- lidé MeSH
- lineární modely MeSH
- mladiství MeSH
- patní kost * MeSH
- tibie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: To assess the prognostic value of sex for non-muscle-invasive/muscle-invasive bladder urothelial carcinoma (NMIBC/MIBC) treated with radical surgery. METHODS: The PubMed, Web of Science, and Scopus databases were searched in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they involved the comparison of the overall, cancer-specific, progression, and recurrence-free survival of patients with NMIBC/MIBC. Formal sex-stratified meta-analyses of these outcomes were performed. RESULTS: Thirty-one studies, which included 32,525 patients with NMIBC, and 63 studies, which included 85,132 patients with MIBC, were eligible for review and meta-analysis. Female sex was associated with worse cancer-specific survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.11-1.31) and overall survival (pooled HR, 1.02; 95% CI, 1.00-1.05) in patients with MIBC. In contrast, however, sex was not associated with cancer-specific survival (pooled HR, 1.01; 95% CI, 0.70-1.46), progression-free survival (pooled HR, 1.04; 95% CI, 0.88-1.24), and recurrence-free survival (pooled HR, 1.06; 95% CI, 0.98-1.16) in patients with NMIBC. CONCLUSIONS: Sex is associated with an increased risk of worse survival outcomes in patients with MIBC but not in those with NMIBC. Given the genetic and social differences between sexes, sex may represent a key factor in the clinical decision-making process.
- MeSH
- karcinom z přechodných buněk * patologie MeSH
- lidé MeSH
- močový měchýř patologie MeSH
- nádory močového měchýře * patologie MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
BACKGROUND: Large-scale analyses addressing cancer-specific mortality (CSM) in T1a renal cell carcinoma (RCC) patients treated with local tumor destruction (LTD), relative to partial nephrectomy (PN), are scarce. OBJECTIVE: To compare CSM after LTD versus PN. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), we identified patients with clinical T1a stage RCC treated with LTD or PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: After 1:1 ratio propensity score matching (PSM) between patients treated with LTD versus PN, competing risks regression (CRR) models addressed CSM, after adjustment for other-cause mortality (OCM) and other covariates (age, tumor size, tumor grade, and histological subtype). RESULTS AND LIMITATIONS: Relative to the 35 984 PN patients, 5936 LTD patients were older and more frequently harbored unknown RCC histological subtype or unknown grade. After 1:1 PSM that resulted in 5352 LTD versus 5352 PN patients, the 10-yr CSM rate was 8.7% versus 5.5%. In multivariable CRR models, LTD was associated with higher CSM, relative to PN (hazard ratio [HR]: 1.58, p < 0.001). Subgroup analyses revealed invariably higher CSM after LTD versus PN in patients with tumor size ≤3 cm (10-yr CSM 7.2% vs 5.3%, multivariable HR: 1.47, p < 0.001) and in patients with tumor size 3.1-4 cm (10-yr CSM 11.4% vs 6.1%, multivariable HR: 1.72, p < 0.001). Lack of information regarding earlier cancer controls, retreatment, tumor location within the kidney, and type of surgery represented limitations. CONCLUSIONS: In T1a RCC patients, LTD is invariably associated with higher CSM relative to PN, even after adjustment for OCM and all available patient and tumor characteristics, and regardless of tumor size considerations. However, the magnitude of CSM disadvantage was more pronounced in LTD patients with tumor size 3.1-4 cm than in those with tumor size ≤3 cm. PATIENT SUMMARY: In patients with small renal masses, we observed higher cancer-specific death rates for local tumor destruction (LTD) than for partial nephrectomy. The LTD disadvantage was more pronounced for patients with tumor size 3.1-4 cm, but was also present in those with tumor size ≤3 cm.
- MeSH
- karcinom z renálních buněk * patologie MeSH
- ledviny chirurgie MeSH
- lidé MeSH
- nádory ledvin * patologie MeSH
- nefrektomie metody MeSH
- proporcionální rizikové modely MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: A growing body of research has incorporated the Social Vulnerability Index (SVI) into an expanded understanding of the social determinants of health. Although each component of SVI and its association with individual-level mental health conditions have been well discussed, variation in mentally unhealthy days (MUDs) at a county level is still unexplored. To systematically examine the geographically varying relationships between SVI and MUDs across the US counties, our study adopted two different methods: 1) aspatial regression modeling (ordinary least square [OLS]); and 2) locally calibrated spatial regression (geographically weighted regression [GWR]). STUDY DESIGN: This study used a cross-sectional statistical design and geospatial data manipulation/analysis techniques. Analytical unit is each of the 3109 counties in the continental USA. METHODS: We tested the model performance of two different methods and suggest using both methods to reduce potential issues (e.g., Simpson's paradox) when researchers apply aspatial analysis to spatially coded data sets. We applied GWR after checking the spatial dependence of residuals and non-stationary issues in OLS. GWR split a single OLS equation into 3109 equations for each county. RESULTS: Among 15 SVI variables, a combination of eight variables showed the best model performance. Notably, unemployment, person with a disability, and single-parent households with children aged under 18 years especially impacted the variation of MUDs in OLS. GWR showed better model performance than OLS and specified each county's varying relationships between subcomponents of SVI and MUDs. For example, GWR specified that 69.3% (2157 of 3109) of counties showed positive relationships between single-parent households and MUDs across the USA. Higher positive relationships were concentrated in Michigan, Kansas, Texas, and Louisiana. CONCLUSIONS: Our findings could contribute to the literature regarding social determinants of community mental health by specifying spatially varying relationships between SVI and MUDs across US counties. Regarding policy implementation, in counties containing more social and physical minorities (e.g., single-parent households and disabled population), policymakers should attend to these groups of people and increase intervention programs to reduce potential or current mental health illness. The results of GWR could help policymakers determine the specific counties that need more support to reduce regional mental health disparities.
- MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- prostorová analýza MeSH
- prostorová regrese * MeSH
- průřezové studie MeSH
- sociální zranitelnost * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Michigan MeSH
INTRODUCTION: Despite the health benefits, a large proportion of girls and boys in Europe do not travel to school actively. A better understanding of the correlates associated with this behavior could guide interventions. This study examines perceived social and environmental correlates of active travel to school (ACTS) from the 2017/18 Health Behavior in School-Aged Children (HBSC) survey in four European countries, with a special emphasis on gender differences (n = 22,023). METHODS: Logistic regression was conducted to analyze associations between the perceived importance of each correlate and ACTS behavior for 11-, 13-, and 15-year-old girls and boys from Germany, Czechia, Poland, and Slovakia. All models were adjusted for age, family affluence, and meeting World Health Organization recommendations for moderate-to-vigorous physical activity. RESULTS: Rates of ACTS significantly differed between girls and boys. In Czechia, 65% of girls and boys traveled to school actively, followed by Slovakia (61.4% girls and 58.4% boys), Poland (57.7% girls and 60.2% boys), and Germany (42.6% girls and 48.6% boys). Girls were less likely to actively travel to school compared to boys (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.87-0.97). Increasing age (OR: 0.95, 95% CI: 0.93-0.97) and a greater distance to school index (OR: 0.89, 95% CI: 0.88-0.90) were both negatively associated with ACTS. The perceived importance of living closer to school and of road and neighborhood safety was positively associated with ACTS, with a stronger association in boys than in girls for neighborhood safety. On the contrary, the perceived importance of having people to walk with was negatively associated with ACTS, with a stronger association in girls (OR: 0.74, 95% CI: 0.65-0.84) than in boys (OR: 0.77, 95% CI: 0.66-0.88). DISCUSSION: This study provides insights into perceived social and environmental correlates associated with ACTS behavior. Future research should include gender-specific perceptions and more in-depth investigations of correlates encouraging ACTS, especially considering social aspects, safety issues, and the structuring of the environment in different cultural settings.
- MeSH
- chůze * MeSH
- dítě MeSH
- lidé MeSH
- logistické modely MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Německo MeSH
INTRODUCTION: Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published an update on the Global Strategy for Prevention, Diagnosis and Management of COPD, introducing a new classification of chronic obstructive pulmonary disease (COPD). Our aim was to assess the prognostic value of the new GOLD classification system in comparison with the previous GOLD classification systems (GOLD stages I-IV and GOLD groups A-D) and the BODE index. METHODS: We used the data of 784 patients with COPD from the Czech Multicenter Research Database of COPD. Patient survival was analyzed with the use of Kaplan-Meier estimate and Cox model of proportional risks. ROC analysis and area under curve (AUC) were used for comparison of GOLD classifications and BODE index. The analyses were performed with the use of software R (version 4.2.0). RESULTS: We analyzed data of 782 patients with complete data on GOLD classifications. The study population comprised 72.9% of men, 89.1% current or former smokers, with a mean age of 66.6 years, a mean BMI of 27.4 and a mean FEV1 44.9% of predicted. Probability of 5-year survival differed by GOLD classification. Application of the 2023 GOLD classification showed increased risk of death in group B (HR 1.82, 95% CI 1.14-2.92; p = 0.013) and in group E (HR 2.48, 95% CI 1.54-3.99; p˂0.001). The ROC analysis showed that the overall prognostic value of the 2023 GOLD classification was similarly weak to previous A-D GOLD classification schemes (AUCs 0.557-0.576) and was lower compared to the GOLD 1-4 system (AUC 0.614) and even lower when compared to the BODE index (AUC 0.715). CONCLUSION: We concluded that the new GOLD classification system has poor prognostic properties and that specific prediction tools (eg, the BODE index) should be used for mortality risk assessment.
- MeSH
- chronická obstrukční plicní nemoc * diagnóza terapie MeSH
- hodnocení rizik MeSH
- lidé MeSH
- prognóza MeSH
- progrese nemoci MeSH
- proporcionální rizikové modely MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
