Follow-up Study Research Articles

Risk of cancer progression of non-atypical endometrial hyperplasia in a diverse patient population: A long-term, follow-up study

Risk of cancer progression of non-atypical endometrial hyperplasia in a diverse patient population: A long-term, follow-up study

Analysis of different factors on dental students' perception of a flipped classroom model: A 6-year follow-up study.

To evaluate different factors affecting two different cohorts of dental students' perceptions with the flipped classroom (FC) model in a preclinical dental course over six years. In 2016 (cohort #1) and 2022 (cohort #2), second-year dental students participated in FC model in a preclinical dental course consisting of pre-class recorded videos and lectures along with classroom interactive exercises. Students then completed an anonymous pen-and-paper survey evaluating three factors influencing students' overall study experience with the FC model. Survey responses from cohort #1 and cohort #2 were compared to assess the effect of generation, student demographics and COVID-19 pandemic on students' perceptions. When asked to rate the FC experience out of 5, the mean ratings of cohort #1 and cohort #2 were 4.3 (±0.9) and 4.0 (±0.8), respectively. Cohort #2 preferred viewing slides and videos prior to class and had a higher agreement that pre-class course materials were beneficial to class preparation. Conversely, cohort #1 had a higher agreement that in-class discussion and exercises helped them to learn course content. From cohort #2, 88.6% of males and 71.6% of females preferred the FC approach over traditional lecture. Both cohorts reported positively with the FC model of teaching. Cohort #2 had higher positive reports with the pre-class work and cohort #1 had a higher positive report with in-class work. Course design should reflect the students' points of view and learning perspectives with careful consideration of the student population in the classroom.

Labor market participation in people with intellectual disability – a follow-up study in Sweden

Abstract Background Work is vital to people’s health and quality of life. The Convention on the Rights of Persons with Disabilities affirms the right to work on an equal basis with others including an opportunity to earn a living by work, but evidence shows that people with intellectual disability (ID) are at greater risk of unemployment and social exclusion. Due to the lack of comprehensive data for longitudinal follow-ups, information on long-term labor market participation (LLMP) in people with ID is scarce. This study aimed to investigate factors of importance for LLMP in individuals with ID in Sweden. Methods The study was based on data from the upper secondary school for pupils with ID between 2001 and 2020 (N = 26,905) and from the longitudinal integrated database for health insurance and labor market studies. A sample of gainfully employed in 2011 (n = 2,719), was followed with respect to LLMP until 2020. Odds ratios (ORs) with 95% confidence intervals (CI) for associations between educational, sociodemographic, and work factors and LLMP (i.e. gainful employment throughout the follow-up), were estimated stratified on sex. Results LLMP was twice as likely in men compared with women, OR 2.06 (1.78-2.58) as was work in the private sector. Factors of significance for LLMP in men and women alike were: completed national education program, OR 3.40 (3.06-3.86) and OR 2.91 (2.40-3.54), parents’ education; compulsory school in mothers’, OR 1.22 (1.06-1.41) and 1.24 (1.00-1.55) and in fathers’ OR 1.35 (1.17-1.56) and 1.49 (1.20-1.85), while municipality of residence was significant only in men, OR 1.30 (1.10-1.56). Conclusions Public health prevention for disadvantaged groups requires accurate and up-to-date knowledge. Using unique register-based data, this is the first study on LLMP in people with ID in Sweden. Knowledge on what social determinants may strengthen LLMP is important since limited LLMP increases the risk of missing out on health benefits that employment may offer. Key messages • There was a significant gender difference in long-term labor market participation in people with intellectual disability in Sweden. • There is a need for increased knowledge on what social determinants may strengthen long-term labor market participation in people with intellectual disability.

Evaluation of the Beneficial Parenting Partnership Model Assimilation in Parent-Infant Centers

Abstract Background The Beneficial Parenting Partnership (BPP) model is being implemented in Parent-Infant Centers (PIC) across Israel to improve the partnership skills of PIC nurses when working with parents, promote child development, and enhance parental well-being. This initiative is being led by the Israeli Ministry of Health, Goshen NGO, and Lotem company and is supported by the Yad Hanadiv and Bernard van Lear foundations. Methods The first data collection (T1) was held from December 2022 to January 2023 among 706 parents of children aged two weeks to 36 months (M = 8.17 months, SD = 7.48) who visited one of 18 PICs. Research assistants approached the parents and asked for their agreement to fill in the study questionnaire. Of these, 328 parents agreed to participate in the follow-up study (T2) held in January-February 2024 using a telephone survey. Differences in the parent’s satisfaction, visit experience, and parental well-being were assessed using parried sample T-tests. A linear regression model was calculated to assess the factors predicting the increase in the parent’s visit satisfaction. Results Significant differences were measured between T1 and T2 in parental satisfaction (M = 4.51 and 4.71 retrospectively, P < 0.001), parental positive visit experience (M = 4.58 and 4.68 retrospectively, P = 0.019), and parental well-being (M = 3.81 and 3.97 retrospectively, P < 0.001). Findings suggest a marked improvement in satisfaction, visit experience, and reported well-being after a year of BPP model assimilation among PIC nurses. The regression model, explaining 42% of the variance in increased parental satisfaction, indicated that a higher increase could be predicted by a higher increase in positive visit experience and a higher trust level in the PIC nurse at T1. Conclusions The BPP model’s assimilation among Israeli PIC nurses was successful, resulting in improved parent experience, satisfaction, and well-being. Key messages • The Beneficial Parenting Partnership model is well-suited for implementation among nurses working with parents of babies and toddlers to promote collaborative nurse-parent communication. • During routine meetings at Parent-Infant Centers, nurses can act as a catalyst for promoting parental well-being.

Ambulatory polygraphy as a screening tool for obstructive sleep apnea in combination with semi-continuous rhythm monitoring in patients with atrial fibrillation: a pilot study

Abstract Background Obstructive sleep apnea (OSA) is a common, yet underdiagnosed risk factor in atrial fibrillation (AF) patients. Polysomnography (PSG) is the gold standard for OSA diagnosis but is also costly, time-consuming, and labor-intensive. (Cardio)-respiratory polygraphy (PG) offers an ambulatory screening for OSA detection. Studying the impact of OSA diagnosis and treatment on AF recurrence will require scalable tools for semi-continuous heart rhythm monitoring. Purpose The NOXFib-AF pilot study assessed the feasibility of PG as an OSA screening tool in patients with AF. The study monitored AF recurrences using a Fitbit smartwatch for heart rhythm monitoring with the FibriCheck algorithm. This pilot assessed the feasibility and patient compliance. Methods Overnight OSA testing was performed with the Noxturnal T3 (NOX-T3s) PG device used at home by AF patients, followed by four weeks of heart rhythm monitoring. Both semi-continuous monitoring with the Fitbit Versa 2 smartwatch with FibriCheck algorithm, and spot-check measurements on a smartphone (twice daily and in case of symptoms) were used. Patients with OSA suspicion on PG (Apnea-Hypopnea Index (AHI) cut-off ≥ 11.1 based on previous studies) were referred for PSG confirmation. Patient satisfaction with the PG and Fitbit smartwatch was evaluated through questionnaires. Results Thirty symptomatic AF patients underwent an overnight PG-based OSA screening, achieving an overall success rate of 96.7% (29/30). Interim analysis of 19 patients who underwent PSG evaluation upon referral showed that 12 (63.2%) were correctly diagnosed with at least moderate OSA (i.e., AHI ≥ 15) and were eligible for reimbursed CPAP treatment. PG and PSG agreement for OSA classification was fair (Cohen’s kappa = 0.230), with 68.4% (13/19) correctly classified (normal-mild, moderate-severe). There was high patient adherence to wearing the smartwatch for four weeks, with median compliance (i.e., adherence to the expected number of measurements) of 96.9% (IQR: 94.3% – 97.6%). A median of 150 (IQR: 145 – 151) daily automatic measurements were performed. Spot-check measurements via the smartphone also showed high compliance (110%, IQR: 100.0% – 135.5%) and high patient motivation (i.e., consistency of performing measurements; 90.3%, IQR: 67.7% – 96.8%). Patients were positive for both PG screening (Figure 1A) and Fitbit-based FibriCheck monitoring (Figure 1B). Conclusions PG is a feasible approach as a home screening tool for OSA, positively perceived by patients. Also, the acceptance of semi-continuous Fitbit-based FibriCheck monitoring was high. In a follow-up study, both tools will be used to evaluate the impact of a structured OSA screening and treatment trajectory on AF burden.

Arterial stiffness for predicting major adverse cardiovascular events in post-infarcted patients

Abstract Introduction According to recent 2021 ESC prevention guidelines arterial stiffness (aortic pulse wave velocity –PWV, augmentation index - Aix) predicts future major adverse cardiovascular events (MACE). Both parameters have a prognostic relevance in different patient population (hypertension, diabetes, chronic kidney disease), however in post-infarcted, very high cardiovascular risk population the exact prognostic value for PWV and Aix needs to be clarify. Purpose We evaluated PWV and Aix cut-off values for MACE prediction and validated the prognostic relevance of high stiffness parameters in post-infarcted patients. Methods Oscillometric based pulse wave analysis method (Arteriograph) was applied for calculating arterial stiffness. We aimed to evaluate PWV and Aix cut-off values for predicting MACE (comprising all-cause death, non-fatal myocardial infarction, ischemic stroke, hospitalization for heart failure and coronary revascularization) in post-infarcted, very high cardiovascular risk patient population. 114 patients (89 male, average age: 62,5±10,5 years) were investigated in this long term, median 16,2 (IQR: 6,5-17,4) years follow-up study. Results Strong, significant correlation was found between PWV and Aix values (Spearman rho: 0,648, p<0,001). Totally 140 MACE events occurred during the 16,2 years follow-up period. Optimized PWV and Aix cut-off values for MACE prediction were calculated (PWV: 9,84 m/s, AUC: 0,754 (95% CI: 0,66-0,85), p<0,001; Aix: 34,8 %, AUC: 0,67 (95% CI: 0,57-0,77), p<0,05) by ROC analysis (Figure 1.). Kaplan-Meier analysis in both parameters showed a significantly lower event-free survival in case of high PWV and Aix values (p<0,05; Figure 2.). Multivariate Cox regression analysis revealed PWV and Aix as an independent predictor of MACE (PWV HR: 1,32 (95% CI: 1,15-1,53), p<0,001; Aix HR:1,04 (95% CI: 1,01-1,08), p<0,05). Conclusions Arterial stiffness, particularly elevated PWV predicts MACE in post-infarcted, very high cardiovascular risk patient population. All these findings emphasize the clinical relevance for the future measurement of arterial stiffness might contribute to improve individual risk stratification in patients after myocardial infarction.ROC analysis for the prediction of MACEKaplan-Meier curves for MACE

Relationship of anxiety and depression with smoking cessation treatments: a follow-up study

ABSTRACT Background Smoking is known to be closely associated with a stress levels and anxiety. In this study, the effects of smoking cessation treatments were investigated on anxiety/depression. Methods Socio-demographic characteristics The Fagerström/Test/Nicotine/Dependence, the Hospital Anxiety and Depression (HAD) scale were applied at first time. The first group received “varenicline+counseling,” second group “bupropion+counseling,” and third group “counseling only.” The HAD scores were recorded in quit smokers. Anxiety and depression scores were compared between groups and between smokers and ex-smokers in the first and sixth month. Results Firstly, The HAD scores revealed that anxiety was present in 46.8%, depression in 11.2%, anxiety and/or depression in 48.9%. A significant decrease in both anxiety and depression scores was observed in quit smokers at 6 months (47.9% and 37.4%, respectively) (p < .001). At the sixth month, there was a significant decrease in anxiety scores in the varenicline and bupropion groups. In addition, a significant decrease in the depression score was observed in the varenicline group. In the bupropion group, the smoking cessation rate was higher in those with high anxiety and/or depression scores (66.7%). Conclusions Varenicline decreased anxiety/or depression scores in both smokers and quit smokers, whereas quit smoking rate increased in those with anxiety/depression in the bupropion.

EXPRESS: The lexical boost is not an automatic part of sentence production: Evidence from Japanese structural priming.

The lexical boost is an increase in structural priming with overlapping elements like verbs. Residual activation priming theories argue that the boost is an automatic side effect of sentence planning. In contrast, explicit memory theories of the boost argue that it is the result of a non-automatic explicit memory retrieval. These theories were contrasted in Japanese by including a prime memory task in a structural priming study. Structural priming was found for both datives and passives, but no lexical boost was found and one possible reason was that explicit memory for the prime structure was weak. In a follow-up study, priming was found in a sentence completion task, but there was no lexical boost. The existence of abstract priming and the lack of a lexical boost in these studies falsifies theories that argue that verb overlap automatically creates a boost under conditions that exhibit abstract priming.

Modification in Quality of Life and Health in Medical Students across Graduation

Abstract Background Medical students experience numerous demands during the education process, determining their quality of life (QoL) and health status. POLLEK study aims to identify and evaluate the quality of life by simultaneously assessing their determinants in Polish medical students during long-term observation. We have also examined the prevalence of chronic diseases, specifically focusing on overweight and obesity, and identified their risk factors. Methods The POLLEK is the follow-up cohort study conducted among medical students at the Medical University of Silesia in Katowice. Students were followed during two observation periods: in their first year of studies, the academic year 2021/2022 (T1), and in their second year, the academic year 2022/2023 (T2). Results The total number of participants in the first year of observation (T1) was 427 while in the second year (T2) was 335. We identified that the QoL score significantly decreased in their second year of studies mainly in the somatic and psychological domain. The determinants of QoL domains common to T1 and T2 remained self-declared health status, frequency of physical activity, and current financial situation. In the initial year of evaluation, 56 students (13.10%) were overweight or obese, and 52 (15.8%) in the second. Regardless of the academic year, the increased risk of being overweight or obese was significantly associated with dissatisfaction with personal health, financial deficiencies, and a diet abundant in animal products. Conclusions The QoL of medical students and selected indicators of their health status deteriorated during the observation period. Our findings suggest that medical schools should actively promote the activity needed to achieve a balance between schoolwork and the personal life of medical students from the beginning of university study. Key messages • Medical students experience numerous demands during the education process, determining their quality of life (QoL) and health status. • Medical schools should actively promote the activity needed to achieve a balance between schoolwork and the personal life of medical students from the beginning of university study.

Can you bear with me? A comparison study of multifaceted discrepancy–brand avoidance relationships between China and the USA

PurposeBrand information is ubiquitous online and offline; consumers exhibit brand avoidance tendencies towards brand stimuli when there is a discrepancy between a brand image/personality and one’s self-concept. Given the multifaceted culturally constituted self-domains and self-importance, this research investigates how cultural variation affects reactions to self-brand discrepancy, considering two types of narcissist orientations.Design/methodology/approachUsing national culture as proxy for cultural orientation, sample data were collected through surveys administered to 410 participants (210 in China and 200 in the USA). A multi-group structural equation model was adopted to examine the conceptual model and proposed hypotheses. The follow-up qualitative study was conducted to allow further discussion of the quantitative results.FindingsThe results show that self-brand discrepancy can only be converted into brand avoidance tendency through the activation of cognitive dissonance for both Americans and Chinese. Specifically, for Chinese consumers only (ideal) social identity self-brand discrepancies can activate avoidance behaviour. In addition, grandiose and vulnerable narcissism orientations co-exist for both Chinese and Americans, these negatively moderate the relationship between social self-brand discrepancies and cognitive dissonance. For US consumers, idealised identity discrepancies mitigate dissonance; only those with a vulnerable narcissistic orientation would act on avoidance when experiencing dissonance.Originality/valueBy incorporating cultural variations in the investigations of self-brand discrepancy, this paper advances existing knowledge on dissonance and coping mechanisms. In addition, by bringing narcissistic orientations to the fore, it allows for a deeper understanding of how these cultural variations operate. In addition, our research provides important guidelines for brand practitioners to better leverage their marketing campaigns in offline and online contexts and to reduce brand avoidance tendencies across the international marketplace.

Phosphorylated tau protein serum levels increase over time in patients with chronic heart failure

Abstract Background/Introduction Amongst various potential biomarkers associated with cognitive deficits, phosphorylated Tau (pTau) appears to link brain and cardiac abnormalities through a systemic tauopathy pathway. Purpose A recent report on the potential importance of myocardial pTau in chronic heart failure (HF) prompted the here described longitudinal quantification of circulating pTau serum levels in patients with HF. We hypothesized that serum pTau accumulates in HF and is associated with markers of myocardial dysfunction. Methods Eligible patients within the prospective, investigator-initiated, monocentric follow-up study Cognition.Matters-HF were older than 18 years, suffered from stable chronic HF and were free from major neurological or psychiatric disorders. Beyond the cardiological assessment including transthoracic echocardiography and six minute walking distance (6-MWD), investigations at baseline, 1 year and 3 years comprised extensive, domain-specific psychological testing and volumetric brain magnetic resonance imaging. Serum pTau was measured using the pTau181 advantage kit. Results Serum samples were available from 78 patients. Mean age was 63±10 years and 87% were men. Serum pTau longitudinally increased from a median of 1.05 (quartiles 0.26, 1.21) pg/ml at baseline to 1.84 (1.36, 3.60) pg/ml after 3 years (p&amp;lt;0.001). During that time period, LVEF, NT-proBNP, 6-MWD and the hippocampal volume remained unaltered, whereas global brain volume and cortical thickness shrank age-appropriately. Cognitive testing revealed that domain-specific T-scores within 36 months remained stable for attentional intensity and executive functioning, and even improved for memory. When we entered baseline values of age and above-mentioned cardiac, brain-volumetric, and cognitive parameters into a multivariable regression model predicting log-transformed pTau, only age (β=0.34), NT-proBNP (β=0.24) and GBV (β=0.26) were independently associated with pTau serum levels (R2=0.18). Consistently, at 36 months, the same predictors were selected by the model (R2=0.29): age (β=0.41), NT-proBNP (β=0.43), and global brain volume (β=0.26). Moreover, higher baseline pTau (β=0.23) and lower 6-MWD (β=-0.39) independently predicted ΔpTau with an explained variance (R2) of 0.24. Conclusions We observed a prominent increase of serum pTau over time, which was predicted by prevalent myocardial dysfunction. Moreover, absolute NT-proBNP levels were independently associated with absolute pTau serum levels, along with age and global brain volume. Mechanistically, phosphorylation of cardiac tau is thought to destabilize its interaction with microtubules causing microtubule detyronisation and increased myocardial stiffness through enhancing the mechanical resistance of contracting cardiomyocytes. The etiological role of pTau in the development of HF and the potential of serum pTau as a novel biomarker of chronic HF warrants further studies.

Left atrial reservoir strain and global longitudinal strain associates with re-hospitalization and mortality in patients admitted for acute heart failure

Abstract Background Left atrial reservoir strain (LAr) and global longitudinal strain (GLS) have emerged as useful parameters for the assessment of left ventricular diastolic function and the estimation of left ventricular filling pressures. Yet, there remains a gap of knowledge regarding the possible association of LAr and GLS with re-hospitalization and mortality in patients with acute heart failure (HF). Aims This study aims to investigate the association between LAr and GLS with re-hospitalization and mortality in patients admitted for acute HF. Methods Out of 526 enrolled patients admitted for acute HF, 142 (mean age 71, 25% women) were systematically evaluated for LAr and GLS using speckle tracking echocardiography. Multivariable Cox regression analyses, adjusting age, sex, current smoking prevalent atrial fibrillation, hypertension, kidney disease and plasma glucose, were used to assess the associations between continuous values of LAr and GLS with all-cause mortality and HF-related re-hospitalization. Results The median follow-up time to death of any cause and HF rehospitalization was 39 (interquartile range 14-66) and 22 (4-51) months, respectively. During follow up, 63 (44%) patients died, and 63 (44%) were re-hospitalized due to HF. Lower values of LAr were significantly associated with higher risk of mortality (HR 0.93; 95%CI 0.89-0.98, p=0.008). Similarly, lower GLS was associated with higher risk of mortality (HR 0.94; 95%CI 0.89-0.99, p=0.045). Only lower values of LAr were associated with higher risk of HF re-hospitalization in the multivariable model (HR 0.93; 95%CI 0.88-0.98, p=0.004). Conclusion In this prospective, long-term follow-up study of patients with acute heart failure, lower values of LAr and GLS showed prognostic significance, with lower values being indicative of poorer outcomes. Notably, LAr was associated with higher risk of both death and rehospitalization for heart failure, whereas GLS was solely associated with higher mortality risk. These echocardiographic parameters could be further investigated for risk assessment of patients with heart failure in order to identify those at higher risk of rehospitalization and death, thereby facilitating targeted interventions to improve their prognosis.KM-curves for or the Quartiles of LAr

Rivaroxaban or warfarin in atrial fibrillation and coronary stent implantation in real-world patients involving chronic kidney disease (REWRAPS): 5-year follow-up study

Abstract Background Recent guidelines recommended either non vitamin K antagonist oral anticoagulants (NOAC) or vitamin K oral anticoagulant (VKA) one year after coronary stenting in patients with atrial-fibrillation (AF). However, whether NOAC is still superior to VKA at 5-years in patients involving chronic kidney disease (CKD) with AF and coronary stenting &amp;gt;1-year remains unclear. Methods In a multicenter, prospective, non-randomized registry, 493 patients were treated with either rivaroxaban or warfarin, while the majority (66.3%) of them had CKD. The primary efficacy endpoint was major adverse cardiac and cerebral events (MACCE). The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium [BARC] 3 and 5). Net adverse clinical events (NACE) were defined as the composite of all-cause mortality and major bleeding. Both crude and propensity score matched (PSM) analyses were performed. P &amp;lt;0.05 was considered as statistically significant. Results At a median follow-up of 4.8 years MACCE rates did not differ between rivaroxaban and warfarin in 486 patients with crude-analysis (23.0% versus 29.0%, hazard-ratio [HR], 0.79; 95% confidence interval [CI], 0.55 to 1.11; P=0.17), while in 316 patients with PSM-analysis rivaroxaban met non-inferiority criteria to warfarin (HR, 0.86; 95% CI, 0.56 to 1.33; p=0.020 for non-inferiority). Rivaroxaban was associated with lower major bleeding risk compared with warfarin (6.5% versus 12.6%; HR, 0.50; 95% CI, 0.27 to 0.91; P=0.025) at crude analyses, which was no longer significant at PSM analyses (5.7% versus 10.8%; HR, 0.53; 95% CI, 0.24 to 1.19; P=0.12). However, NACE rates were significantly lower in rivaroxaban compared to warfarin at both crude (19.0% versus 35.7%; HR, 0.50; 95% CI, 0.35 to 0.72; P=0.0002) and PSM-analyses (19.6% versus 31.0%; HR, 0.63; 95% CI, 0.40 to 0.98; P=0.043), respectively. Conclusions Rivaroxaban did not differ from warfarin for efficacy endpoints of MACCE but was associated with lower NACE rates (i.e. all-cause mortality and major bleeding) in AF and coronary stent in real-world patients having CKD at 5-year follow-up (NCT02024230).

Sex-specific associations between remnant cholesterol and cardiovascular risk in patients undergoing percutaneous coronary intervention: a 5-year large-sample study from the real world

Abstract Background Differences in the pathophysiological characteristics and cardiovascular risk between female and male patients with coronary artery disease (CAD) are well-established. Recent studies on the relationship between remnant cholesterol (RC) and cardiovascular risk in coronary artery disease patients have gained popularity. To date, little is known about the RC-related cardiovascular risk disparities between males and females. Purpose The aim is to investigate sex-specific differences in the association between RC and cardiovascular risk among CAD patients undergoing percutaneous coronary intervention (PCI). Methods A prospective cohort study was conducted among 10,724 CAD patients undergoing PCI from January to December in 2013. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and ischemic stroke) and the secondary outcomes were each component of MACCE. Results Among 9,587 PCI patients included (the average age was 58.43 ± 10.26 years and 2,181 (22.70%) were female), 1,864 (19.4%) MACCEs were recorded during the 5-year follow-up. For primary outcome, a significant interaction was observed between RC levels and sex (P for interaction = 0.007 and 0.011, for continuous and categorical RC variables, respectively). Specifically, in male patients, no significant MACCE risk was observed at any RC level (both P &amp;gt; 0.05) (Figure 1). However, in female patients, both continuous RC levels (hazard ratio [HR] 1.412, 95% confidence interval [CI] 1.103-1.807) and the upper two quartiles of RC relative to the lowest quartile (Q3: HR 1.458, 95% CI 1.062-2.001; Q4: HR 1.496, 95% CI 1.081-2.070) were associated with higher MACCE risk. For secondary outcomes, higher RC levels were linked to an increased risk of cardiac mortality and revascularization in female patients but not in males (Table 1). Conclusions In a large-scale 5-year follow-up study from the real world, we are the first to demonstrate that RC-related cardiovascular risk is specifically observed in female CAD patients undergoing PCI, suggesting that female patients merit closer surveillance and more aggressive RC management to reduce cardiovascular risk.

Novel metabolomic predictors of incident colorectal cancer in men and women.

Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk. We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995. Over 22.9 years, 684 (409 NHS, 275 HPFS) incident CRC cases occurred and were matched 1:1 to controls. Liquid chromatography-mass spectrometry (LC-MS) identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis (MSEA) was used to identify differential abundance in metabolite classes. Weighted Correlation Network Analysis (WGCNA) provided modules of covarying metabolites, which were tested for CRC association. MSEA identified specific acylcarnitines associated with higher CRC risk and triacylglycerols with lower CRC risk among women and men. Further, phosphatidylcholines were associated with a higher risk of CRC among men. In an analysis restricted to CRC cases diagnosed two years after blood draw, myristoleic acid (OR = 1.37; 95%CI = 1.15-1.62; FDR = 0.072) and C60:12 triacylglycerol (OR = 0.75; 95%CI = 0.64-0.88; FDR = 0.072 were associated with CRC risk in women. WGCNA identified amino acids associated with CRC in men, fatty acid esters (carnitines) with distal CRC in men, and triradylcglycerols inversely associated with CRC in women. We identified pre-diagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.

Effects of body mass index on worsening of heart failure and all-cause death in patients with heart failure and reduced left ventricular ejection fraction: a 10-year follow-up study

Abstract Background/Introduction Obesity in patients with heart failure (HF) with reduced ejection fraction (HFrEF) is common, and with the emergence of effective anti-obesity drugs, a better understanding of the relation between BMI and clinical outcome in HFrEF is needed. Purpose This study aimed to analyse whether a body mass index (BMI) above 27 kg/m2 (cut-off used in trials) is associated with a greater rate of all-cause death and HF hospitalization in patients with HFrEF. Methods We included 1,017 medically optimized according to existing HF guidelines at the time and clinically stable HF patients with a left ventricular ejection fraction of &amp;lt;45% from the NorthStar study. Patients were included between 2005 and 2009 and followed for 10 years using Danish nationwide registries. The outcomes of interest were all-cause death and hospital discharge for HF (overnight stay). Descriptive statistics were grouped according to tertiles of BMI. The association between BMI as a continuous variable and the outcomes of interest was analysed using restricted cubic splines in Cox proportional-hazards models. Reported were hazard ratios (HR) with 95% confidence intervals (CI) adjusted for relevant prognostic covariates (reference: BMI = 27 kg/m2). Results At enrolment, the median age was 69 years, 75% were men, and the median BMI was 26.3 kg/m2 (Table 1). Patients in the upper 3rd BMI tertile were younger (median age 67), had a lower level of NT-proBNP level (median 737.5 pg/ml) and a higher proportion of diabetes (29.9%). During 10 years of follow-up, HF hospitalization occurred in 683 patients (61.7%), and 623 patients died (56.3%). A BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization (significantly from BMI 35.2 kg/m2: HR 1.30 [CI 1.00-1.68]; Figure 1). Similar findings were observed for all-cause mortality (significantly from BMI 35.7 kg/m2: HR 1.27 [CI 1.00-1.62]) Conclusion In patients with HFrEF, a BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization and all-cause death. Efforts to find effective and safe approaches to reducing weight in obese patients with HFrEF are warranted.Figure 1

Lipoprotein(a) and cardiovascular prognosis of familial dyslipidemias: data from a 10-year follow-up study

Abstract Background Familial dyslipidemias, such as heterozygous familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) are associated with premature cardiovascular (CV) disease. On the other hand, increased lipoprotein(a) [Lp(a)] is considered as the most prevalent monogenic lipid disorder in the general population. Purpose This study aimed to longitudinally follow up two specific populations with familial dyslipidemias associated with increased CV risk, namely FH and FCH, and compare them with reference to their CV prognosis, investigating in parallel the effect of Lp(a) levels. Methods 433 patients with FH (34% males, mean age 44.2±12.8 years) and 476 patients with FCH (57% males, mean age 49.0±11.1 years) from the outpatient lipid clinic of our hospital, without history of CV disease, who fulfilled the FH and FCH criteria, respectively, participated in the study. Participants were evaluated for a mean follow-up period of 9.6±7.6 years, with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke). Results The incidence of the composite endpoint of major CV events during the follow-up period in the total population was 6.5%, while it was greater in patients with FH compared to patients with FCH (8.1% vs 5.5%, p=0.03). Regarding CV risk factors, FCH compared to FH patients had greater prevalence of baseline hypertension (36% vs 9.7%, p&amp;lt;0.001) and diabetes (11% vs 2%, p&amp;lt;0.001), whereas FH patients had greater Lp(a) levels (37.4±40.3 vs 29.7±34.6 mg/dl, p&amp;lt;0.01). Multiple Cox regression analysis revealed that FH patients had greater CV risk compared to FCH patients (HR 2.17, 95% CI 1.10-4.26, p=0.02). Moreover, in FH patients, increased baseline Lp(a) levels (≥30mg/dl) were an independent predictor of major adverse CV events (HR 2.37 95% CI 1.41-4.90, p=0.02), whereas in FCH patients increased Lp(a) was not an independent predictor. In FCH patients the presence of diabetes at baseline was a strong independent prognosticator of adverse CV events (HR 3.56 95% CI 1.19-11.33, p=0.03), after adjustment for confounding factors. Conclusions FH patients have greater CV risk compared to FCH patients. In FH patients, the presence of increased Lp(a) doubles the CV risk, beyond low density lipoprotein cholesterol levels. On the other hand, in FCH patients the presence of diabetes triples the CV risk, whereas Lp(a) does not convey an independent prognostic value.

Citizen’s perspective on pandemic preparedness

Abstract In the aftermath of COVID-19, pandemic preparedness has become a key concern for governments and public health institutes across the world. As policymakers and scientist grapple with the lessons learned and implications for pandemic preparedness, it is also imperative to take the perspectives of citizens into account. To explore the perceptions and expectations regarding pandemic preparedness, the Behavioural Unit of RIVM conducted a qualitative follow-up study amongst a representative sample of Dutch citizens. At different locations in the Netherlands focus groups were organized with diverse participants. The topic guide was based on an analysis of a previously administered pandemic preparedness questionnaire and theoretical framework, also presented in the current workshop. Topics included risk perceptions, trust in government and other institutions versus self-reliance and the role of media and communication. Furthermore, pandemic preparedness was contrasted with other forms of disaster and crisis management. During the presentation the latest results are shared, and we will discuss possible policy recommendations and how the general public can be involved to develop a better understanding of their needs with respect to preparedness.

Associations between biomarkers and P-wave indices in patients with heart failure

Abstract Background Atrial structural abnormalities linked to the risk of atrial fibrillation (AF), as indicated by P-wave indices on surface ECG, are associated with the fibrotic transformation of the atrial myocardium. To what extent incident AF can be predicted by ECG characteristics in patients with advanced atrial structural remodeling, such as patients with heart failure (HF), is less well studied. Purpose To evaluate the association between P-wave indices and biomarkers implicated in cardiac fibrosis, and incident AF in patients with HF. Methods Patients with new-onset or worsening of HF were prospectively recruited in a observational study (n=501) and followed-up for 5 years. Blood samples were collected for analysis using proximity extension assay that included a subset of biomarkers that were associated with fibrosis development (TIMP-2, MMP-2, MMP-3, MMP-9, ST-2, GDF-15, Gal-3). All ECGs ever recorded in the hospital catchment area were exported in digital format and processed using Glasgow algorithm for calculation of the P-wave indices (P-wave duration [PWD], P-wave terminal force in V1 [PTFV1] and P-wave axis [Paxis]) and rhythm identification. AF diagnosis was ascertained by manual ECG review. Only patients who did not have AF reported or ECG documented at enrolment were included in the analysis. Of those subjects, 121 patients also had biomarkers of fibrosis analyzed. Cox-regression analyses were used to assess biomarkers’ and p-wave indices’ associations with incident AF. Results After exclusion of patients with prevalent AF (n=317), 184 patients comprised the study group (mean age of 71 years, 33.2% women, 121 patients with biomarker data available). During follow-up, incident AF was observed in 39 patients. At enrolment, PWD&amp;gt;120 ms was observed in 38.7%, abnormal PTFV1&amp;gt;40 mm*ms in 24.5% and Paxis&amp;lt;0° in 5.4%. Among the seven biomarkers assessed, five demonstrated significant associations with incident AF in adjusted analyses: TIMP4 (HR 1.78; 95%CI 1.03-3.05; p=0.037); MMP2 (HR 1.97; 95%CI 1.03-3.80; p=0.042), MMP3 (HR 1.39; 95%CI 1.03-1.88; p=0.031); ST2 (HR 1.91; 95%CI 1.29-2.83; p=0.001) and GDF-15 (HR 2.56; 95%CI 1.50-4.35; p=0.001) (Figure 1). However, none of the tested P-wave variables (P-wave duration, P-wave terminal force, and P-wave axis) were associated to incident AF. Conclusions In this prospective long-term follow-up study of patients admitted for acute HF, biomarkers with proven associations to fibrosis were strongly associated with incident AF. P-wave indices used for prediction of AF in epidemiological cohorts appear to have limited value in patients with HF who have high prevalence of ECG atrial abnormalities at baseline.

Sleep characteristics in relation to cardiovascular disease incidence and mortality in individuals with diabetes

Abstract Background/Introduction Evidence regarding the potential health effects of sleep characteristics among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine sleep characteristics in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease (CHD), and stroke, and all-cause and cause-specific mortality among individuals with T2D. Methods We prospectively followed 21,902 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1986-2018, Health Professionals Follow-Up Study: 1986-2018). Sleep characteristics, including sleep duration, snoring, sleep apnea, and sleep quality, were repeatedly assessed using self-reported questionnaires at baseline and follow-up. Associations of sleep characteristics with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographic, dietary and lifestyle factors, and medical history. Results During 170,355 and 196,458 person-years of follow-up in participants with T2D, there were 2,486 incident CVD events and 3,922 deaths, respectively. Compared with sleeping for 7-8 h/day, the multivariable-adjusted hazard ratios (HRs) of sleeping for ≤5 h/day were 1.21 (1.02, 1.45) for CVD incidence, 1.24 (1.20, 1.51) for CHD incidence, 1.40 (1.24, 1.58) for total mortality, 1.52 (1.20, 1.92) for CVD mortality, and 1.27 (1.01, 1.61) for other non-CVD and non-cancer mortality, while the HRs of ≥10 h/day were 1.42 (1.21, 1.66) for total mortality, and 1.63 (1.20, 2.10) for other non-CVD and non-cancer mortality. Furthermore, compared with participants without habitual snoring, those with habitual snoring had a 21%, 24%, 18%, and 33% higher risk for CVD incidence, CHD incidence, CVD mortality, and total mortality, respectively. Compared with participants without diagnosed sleep apnea, those with sleep apnea had a 27%-58% higher risk for CVD incidence, CVD mortality, and total mortality. In addition, lower habitual sleep quality, including sleep difficulties and restless sleep, was associated with a substantially higher risk of CVD, CHD, or CVD mortality. No associations were observed between sleep characteristics with risk of stroke and cancer mortality in individuals with T2D. Conclusions Short and long sleep durations as well as habitual snoring, sleep apnea, and lower sleep quality were independently associated with higher risks of CVD incidence and mortality, particularly CVD mortality in individuals with T2D.