Analysis Of Outcomes Research Articles

Beyond School Climate: Validating the School as a Protective Factor-Brief Survey.

The conceptual framework for School as a Protective Factorapproach was presented in a companion article in this issue of the journal. The current article describes the validation of the School as a Protective Factor-Brief (SPF-Brief), a 13-item survey measuring the 3 core constructs and 13 defining characteristics of this framework. The SPF-Brief was validated through 2 studies. The developmental study used a longitudinal design including 1349 participants who completed surveys over 5 semesters, while the validation study used a cross-sectional design with 2775 participants. Both studies included middle and high school students. Factor analysis, growth model analysis, criterion-related validation, and outcome analysis were employed. Analyses provided strong evidence supporting the reliability and validity of the instrument and conceptual framework. Higher SPF-Brief scores were associated with higher math grades, English grades, and quality of life, as well as lower rates of anxiety, depression, conduct disorder, alcohol, e-cigarette, tobacco, and cannabis use. Effect size estimates ranged from moderate to strong. These findings suggest the utility of the SPF-Brief instrument and the School as a Protective Factor framework. Together, they may offer advantages to the traditional school climate approach.

Gynecologic oncology robot-assisted surgery in octogenarians: Impact of age on hospital stay.

To compare postoperative stay in octogenarians and younger patients undergoing gynecologic oncology robot-assisted surgery. A retrospective review of robot-assisted surgery in Gynecological Oncology division during 2019-2022. We included all consecutive cases. Octogenarians (age ≥80 years) and younger patients were investigated by univariable analysis for characteristics and outcome. A total of 816 robot-assisted surgeries were performed, 426 (52.2%) endometrial cancer, 159 (19.5%) ovarian cancer, 27 (3.3%) cervical cancer, 35 (4.3%) endometrial intraepithelial neoplasia, and in 169 (20.7%) the final pathology was benign. There were 60 (7.4%) octogenarians and 756 (92.6%) younger patients. The proportion of patients with an American Society of Anesthesiology score greater than 2 was higher among octogenarians (66.7% vs 32.0%, P < 0.001). The median console time, surgical time, and total operation theater time were similar between groups (P = 0.303, P = 0.643 and P = 0.688, respectively). Conversion rate did not differ between groups (0.4% among younger patients vs 0% in octogenarians, P > 0.99). The median length of stay in the recovery room was similar in both groups (median 170 min, interquartile range [IQR] 125-225 min vs 170 min, IQR 128-240 min in octogenarians, P = 0.731). Length of hospital stay was similar in both age groups; median 1 day (IQR 1-1) among octogenarians versus 1 (0-1) in younger patients (P = 0.136). Octogenarians undergoing robotic surgery have no increased risk of length of stay or conversion to laparotomy compared with younger patients.

Analysis of Pregnancy Outcomes in Patients Exhibiting Recurrent Miscarriage With Concurrent Low-Titer Antiphospholipid Antibodies.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal-fetal complications in patients with low-titer aPLs. The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (n = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (n = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal-fetal complications were subsequently compared. The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (p < 0.05) and a higher ANA positivity rate (p < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (p < 0.05). Post treatment, the live birth rate in the low-titer group significantly exceeded that of the untreated group (67.6%vs. 33.3%; p = 0.005). The miscarriage rate was notably lower in untreated low-titer patients compared to aPLs-negative patients (32.4%vs. 66.7%; p = 0.005). No significant differences were observed in maternal or fetal complications between the groups. In the standard treatment group (Group A), there were 8 (53.3%) live births, whereas the multidrug treatment group (Group B) had 40 (71.4%) live births, a significantly higher rate than in the standard treatment group, although the difference lacked statistical significance. The study indicates that untreated RM patients with low-titer positive aPLs have a higher recurrence of miscarriage compared to the aPLs-negative RM group. However, recurrence significantly decreases following appropriate intervention, suggesting the benefits of treatment for RM patients with low-titer aPLs.

Spatiotemporal Ecologic Analysis of COVID-19 Vaccination Coverage and Outcomes, Oklahoma, USA, February 2020-December 2021.

Data on COVID-19 cases, deaths, hospitalizations, and vaccinations in Oklahoma, USA, have not been systematically described. The relationship between vaccination and COVID-19-related outcomes over time has not been investigated. We graphically described data collected during February 2020-December 2021 and conducted spatiotemporal modeling of monthly increases in COVID-19 cumulative death and hospitalization rates, adjusting for cumulative case rate, to explore the relationship. A 1 percentage point increase (absolute change) in the cumulative vaccination rate was associated with a 6.3% (95% CI 1.4%-10.9%) relative decrease in death outcome during April-June 2021, and a 1.9% (95% CI 1.1%-2.6%) relative decrease in death outcome and 1.1% (95% CI 0.5%-1.7%) relative decrease in hospitalization outcome during July-December 2021; the effect on hospitalizations was driven largely by data from urban counties. Our findings from Oklahoma suggest that increasing cumulative vaccination rates might reduce the increase in cumulative death and hospitalization rates from COVID-19.

Clinical Presentation, Adverse Prognostic Factors and Outcome Analysis of Pediatric Bone Tumors Treated at King Abdullah Specialized Children’s Hospital, Riyadh, Saudi Arabia - A Retrospective Review Over 20 Years

Clinical Presentation, Adverse Prognostic Factors and Outcome Analysis of Pediatric Bone Tumors Treated at King Abdullah Specialized Children’s Hospital, Riyadh, Saudi Arabia - A Retrospective Review Over 20 Years

Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes.

Temozolomide plus PARP inhibition has shown promise in small cell lung cancer (SCLC). We previously reported outcomes from the first 50 patients (cohort 1) of a phase I/II trial of olaparib/temozolomide in recurrent SCLC. Here, we report a final analysis of this trial, including a second cohort with an alternate dosing strategy and an exploratory analysis of CNS-specific outcomes. This was an open-label phase I/II trial testing the combination of olaparib and temozolomide in relapsed SCLC. The primary endpoint was ORR. Secondary endpoints were safety, PFS, and OS. We tested escalating doses of olaparib/temozolomide across two cohorts, both of which had temozolomide dosed on D1-7 of each 21-days cycle. In previously published cohort 1, olaparib was dosed on D1-7; in cohort 2 olaparib was dosed continuously. Sixty-six patients were enrolled across the two cohorts, 50 in cohort 1 and 16 in cohort 2. The confirmed ORR of cohort 1 was 41.7% (20/48 evaluable), and the confirmed ORR of cohort 2 was 7% (1/14 evaluable; closed after dose escalation to enrollment for lack of observed efficacy). Among 15/66 patients (22.7%) with untreated brain metastases at enrollment, best overall intracranial response was CR in 6/15 patients, PR in 4/15 patients, and SD in 3/15 patients for a CNS disease control rate of 87% (95% CI: 59.5-98.3%). Olaparib/temozolomide may be effective in relapsed SCLC, especially for patients with CNS disease. Ongoing analyses regarding optimal dosing schedule will inform potential for future use of this combination in SCLC.

Expert consensus on pharmacoeconomic evaluations alongside clinical trials (2024 edition)

As a technical tool to guide the optimal allocation of healthcare resources, pharmacoeconomic evaluation has been gradually applied to national healthcare decisions, including the adjustment of the National Reimbursement Drug List in China. With the acceleration of drug market approval and access to insurance coverage, the demand for pharmacoeconomic evaluation in healthcare decision-making is also increasing. Designing a pharmacoeconomic evaluation alongside clinical trials has become an important research direction and the source of evidence. In order to facilitate the standardization of this research field, the current consensus focuses on the topic of how to conduct a pharmacoeconomic evaluation alongside clinical trials from the Chinese healthcare system and decision-making context. The consensus group reconciled expert opinions and developed recommendations covering the entire process of study design, data collection and management, data analysis, and methods and results reporting. A total of 24 recommendations regarding to methodology and practice were developed from eighteen aspects including target population, selection of comparators, calculation of sample size, data collection of healthcare resource utilization, data collection of health-related quality of life, cost analysis, health outcome analysis, addressing the missing and censored data, etc., with the aim to provide reference for scholars and decision makers in this research filed.

Addressing Semantic Variability in Clinical Outcome Reporting Using Large Language Models

Background/Objectives: Clinical trials frequently employ diverse terminologies and definitions to describe similar outcomes, leading to ambiguity and inconsistency in data interpretation. Addressing the variability in clinical outcome reports and integrating semantically similar outcomes is important in healthcare and clinical research. Variability in outcome reporting not only hinders the comparability of clinical trial results but also poses significant challenges in evidence synthesis, meta-analysis, and evidence-based decision-making. Methods: This study investigates variability reduction in outcome measures reporting using rule-based and large language-based models. It aims to mitigate the challenges associated with variability in outcome reporting by comparing these two models. The first approach, which is rule-based, will leverage well-known ontologies, and the second approach exploits sentence-bidirectional encoder representations from transformers (SBERT) to identify semantically similar outcomes along with Generative Pre-training Transformer (GPT) to refine the results. Results: The results show that the relatively low percentages of outcomes are linked to established rule-based ontologies. Analysis of outcomes by word count highlighted the absence of ontological linkage for three-word outcomes, which indicates potential gaps in semantic representation. Conclusions: Employing large language models (LLMs), this study demonstrates its ability to identify similar outcomes, even with more than three words, suggesting a crucial role in outcome harmonization efforts, potentially reducing redundancy and enhancing data interoperability.

Cardio-renal syndromes in patients admitted with ST-elevation myocardial infarctions: Incidence and impact on renal and overall outcome

Abstract Background The importance of cardiorenal syndromes (CRS) in patients with heart failure has been shown in many studies. However, there is little data on the impact of a combination of heart failure and renal disease in patients with acute myocardial infarctions. Aim of the present study was to investigate, how often a combination of heart failure (HF) and kidney disease (KD) could be detected in patients with ST-elevation myocardial infarctions and to estimate its impact on outcome. Methods All patients from a German heart center, admitted with STEMI between 2006 and 2022 were analysed. CRS was defined as a combination of heart failure (HF: left ventricular ejection fraction (LV-EF&amp;lt;40%), HF) and kidney disease (KD: GFR at admission &amp;lt;60 ml/min). Patients were assigned in a 2x2 model: HF-/KD-, HF-/KD+, HF+/KD-, HF+/KD+. Outcome analysis was adjusted by confounders in a multivariate Cox-regression-model. Acute kidney injury (AKI) was calculated by AKIN-criteria (KDIGO) Results Of a total of 8276 STEMI-patients included in the study 5696(69%) had a preserved LV-EF and no KD (HF-/KD-), 1354 (16%) a preserved LV-EF and KD (HF-/KD+), 743 (9%) a reduced LV-EF and no KD (HF+/KD-) and 483 (6%) both a reduced LV-EF and KD (HF+/KD+, CRS-Group). In the CRS-group patients were on average older (74.2±12 yrs. vs. 60.8±13 yrs., p&amp;lt;0.01), more likely to be female (36.9% vs. 23.1% in the control group, p&amp;lt;0.01) and more likely to be diabetics (31.0% vs. 16.8% in the control group, p&amp;lt;0.01). CRS was associated with higher rates of cardiogenic shock (41.5% vs. 8.7% in the control group) and higher rates of subsequent AKI with a 18x higher risk to develop AKIN-3 with or without the need for renal replacement therapy (RRT), (table, upper part). In patients with CRS in 11% of patients a temporal RRT was necessary vs. 0.5% in controls. Furthermore, in CRS-patients in-hospital and 1 year-mortality-rates were markedly higher (table, lower part). When adjusting outcomes for confounders (age, gender, CS, diabetes, anterior STEMI, 3 VD) the detrimental effect of CRS on outcome remained: AKIN-3/RRT: OR 16.5, 95% CI 7.5-30.0, p&amp;lt;0.01, In-hospital-mortality: OR 14.2, 95% CI 7.8-21, p&amp;lt;0.01, 1-year-mortality: HR 10.5, 95% CI 7.5-14.1, p&amp;lt;0.01. Conclusions In this analysis of registry data, cardiorenal disease could be detected in 6% of STEMI-patients, with higher rates in women and in diabetics. Patients with cardiorenal disease showed a more than 18-fold higher risk of suffering severe renal failure during the index event and a 24-fold higher risk of in-hospital death. Patients with either heart failure or renal disease were situated between the CRS and control group with regard to outcome. These results underline the additive effects of cardiac and renal disease.Table:Event rates by HF and KD group

Detection and risk stratification of cardiac amyloidosis patients by integration of imaging and non-imaging data using a machine learning approach

Abstract Background With the advent of amyloid-targeting therapies, early and reliable diagnosis as well as precise risk estimation of cardiac amyloidosis (CA) have become of substantial importance. While the current diagnostic approach relies on difficult-to-standardize, visual interpretation of 99mTc-scintigraphy, risk assessment is largely based on a combination of blood and imaging parameters. Purpose Aim of this study is to assess the possibility of machine learning-based integration of scintigraphy, echocardiography, and non-imaging parameters such as blood parameters and comorbidities for the detection and risk stratification of patients with CA. Methods This study included all patients who underwent 99mTc-scintigraphy at a university affiliated tertiary care centre between 2010 and 2023. Two machine learning models were developed, and the relative predictive importance of their parameters were assessed (Figure 1): First, a model to detect patients with CA-suggestive uptake (Perugini grade 2/3) on 99mTc-scintigraphy scans; Second, a model to assess the risk of patients with CA-suggestive uptake for future heart failure hospitalization (HFH). A total of 58 features were extracted from electronic health records including blood, echocardiographic, demographic parameters and comorbidities. Scintigraphy imaging features were extracted from the raw imaging data using a deep learning approach. For the time to HFH prediction, a random survival forest machine learning model was employed. Results Overall, 12 380 consecutively enrolled patients were included, 279 (2.3%) of which were affected by CA-suggestive uptake. The machine learning model showed higher accuracy for the detection of CA (AUC 0.96 [95% CI 0.95-0.97], sensitivity 0.78 [95% CI 0.77-0.80] and specificity 0.99 [95% CI 0.99-0.99]. In the outcome analysis, the machine model showed good accuracy in predicting future HFH (C-index 0.71 [95% CI 0.68-0.75]). Parameter importance for the time to event analysis revealed right ventricular diameter, previous diagnosis of chronic heart failure and creatine kinase as the three most important predictors (Figure 2). Conclusions Detection of patients with cardiac amyloidosis and their risk estimation for heart failure can be aided using machine learning-based integration of imaging and non-imaging data. Our findings may guide novel approaches for assessing disease progression and treatment response.

Bioprosthetic versus mechanical prostheses in patients aged 50 to 70 years undergoing aortic valve replacement surgery: outcomes analysis from propensity score matching

Abstract Introduction Despite increasing use of bioprosthetic surgical aortic valve replacement (bAVR) in patients ≤70 years [1, 2], the relative benefits compared to mechanical valve replacement (mAVR) remain uncertain [3, 4]. Purpose The current study aims to compare mortality and other important clinical endpoints by prosthesis type for patients aged 50-70 years who received an AVR in a well-characterised Australian cohort. Methods A retrospective cohort study was designed utilising the WAVES Patient Registry and incorporating linked administrative outcome data including all patients who had an AVR in Western Australian public hospitals between 2010-2020. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular (CV) mortality, separately and combined with non-fatal myocardial infarction and non-fatal stroke (MACE), major bleeding, and days alive and out of hospital (DAOH). Outcomes were compared based on a propensity-matched analysis (including demographics, biometrics, and clinical characteristics). Results Within the initial cohort of 727 patients undergoing surgical AVR (mean age = 63 ± SD 6), a propensity-matched cohort identified 151 patients each with bAVR (mean age = 61 ± 4) and mAVR (mean age = 60 ± 5). Patients who received mAVR versus bAVR had improved all-cause survival (Hazard Ratio [HR] 0.50; 95% CI 0.25-0.99) but increased risk of major bleeding (HR 4.85; 95% CI 1.57-14.98). There were no significant differences in CV mortality (HR 0.58; 95% CI 0.19-1.74), MACE (HR 0.59; 95 % CI 0.32-1.07), or DAOH by prosthesis type (P = 0.452). Conclusions Patients aged 50-70 years who underwent mAVR had lower risk of all-cause mortality compared with bAVR, despite higher bleeding risk. Although risks of CV mortality and MACE were lower in mAVR, statistical significance was not reached, likely due to the small sample size. Larger studies are necessary to confirm these findings, which have important clinical implications.

Impact of digoxin on gastrointestinal bleeding following left ventricular assist device implantation: a systematic review and meta-analysis

Abstract Introduction Gastrointestinal bleeding (GIB) is a common complication post Left Ventricular Assist Device (LVAD) implantation for patients with advanced heart failure. Recent observational evidence suggested a potential association of digoxin use and GIB reduction post LVAD; however, the proposed benefit remains uncertain. Therefore, we conducted a systematic review and meta-analysis to assess the impact of digoxin use on GIB post LVAD. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the studies published in English exploring GIB with chronic digoxin use following LVAD implantation, till 15/01/2024. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. The primary outcome was all-cause GIB associated with digoxin use in comparison to non-digoxin use. Heterogeneity was assessed using Q test and I2, with I2 &amp;gt; 50% indicating marked heterogeneity. Results A total of three peer-reviewed observational studies (n= 14277) were included in the analysis of the primary outcome. More than 50% of patients received ACE inhibitors/angiotensin receptor blockers. Digoxin use post LVAD was associated with similar GIB incidence in comparison to non-digoxin use (Odds Ratio [OR]= 0.61; 95% CI, 0.33-1.14, I2= 81%, P=0.12), as shown in Figure 1. Interestingly, one study of 199 recipients of LVAD reported significantly lower gastrointestinal angiodysplasia-induced GIB with digoxin use (3% versus 13%, P=0.039). Conclusion Among patients with advanced HF requiring LVAD implantation, the use of digoxin demonstrated similar effectiveness of GIB prevention compared to non-digoxin use. Future studies needed to explore the potential use of digoxin for gastrointestinal angiodysplasia-induced GIB.Figure 1.Forest plot of gastrointestina

Health-related quality of life disparity in cardiac sarcoidosis versus other myocardial diseases

Abstract Background Sarcoidosis, a systemic inflammatory disorder, can manifest as progressive inflammatory heart disease, termed cardiac sarcoidosis (CS). Despite advances in treatment, the impact of CS on health-related quality of life (HRQoL) remains incompletely understood. This study aimed to compare HRQoL between patients with CS and those with non-inflammatory cardiomyopathies, namely dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Purpose To assess and compare HRQoL across patients with cardiac sarcoidosis and non-inflammatory cardiomyopathies. Methods A total of 240 CS patients (86% response rate), 96 DCM patients (55% response rate), and 81 HCM patients (65% response rate) completed the RAND-36 general health-related questionnaire, comprising eight dimensions. Patients listed for transplantation were excluded. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry for CS patients and from medical records in hospitals for HCM and DCM patients. Results Median age ranged from 56 to 59 years across the groups. Unlike DCM, which typically presents with heart failure symptoms, a substantial proportion (82%) of CS patients presented with advanced atrioventricular block or ventricular arrhythmias, while HCM cases were often incidentally detected or identified through family screening. Most CS patients (94%) had implanted pacemakers or ICDs, compared to a lower proportion in HCM (26%) and DCM (63%). DCM patients exhibited a higher prevalence of impaired LVEF (&amp;lt;50%) compared to CS and HCM patients. Functional impairment, as measured by NYHA class, was most pronounced in DCM patients. CS patients experienced more adverse events between diagnosis and the study entry, particularly sustained ventricular tachycardia/ventricular fibrillation. However, heart failure hospitalizations did not significantly differ between groups. Table 1 presents a comparative analysis of patient-reported outcomes across four functional and mental dimensions to assess the relative burden of disease among patients with CS, HCM, and DCM. While the functional dimensions in CS exhibited disparities from both HCM and DCM, no significant differences were observed in the mental dimensions between CS and HCM. CS patients reported lower scores in the domains of role physical, and general health compared to either HCM or DCM counterparts. Conclusion Patients with CS demonstrated significantly poorer HRQoL compared to those with non-inflammatory cardiomyopathies. This underscores the substantial burden of disease associated with CS and highlights the importance of comprehensive management strategies to address both clinical and quality of life aspects in affected individuals.

Aortic valve replacement and mortality with left ventricular hypertrophy in setting of normal LVEF

Abstract Background Without symptoms, indications for aortic valve replacement (AVR) in severe aortic stenosis (AS) differ for individuals with normal vs. low/decreasing left ventricular ejection fraction (LVEF). Conceptually, the development of left ventricular hypertrophy (LVH) could also indicate ventricular injury and potential benefit with earlier AVR. However, little is known about the comparative effectiveness of AVR in individuals with LVH. As such, unlike low or dropping LVEF, development of LVH is not in itself an indication for AVR in clinical guidelines. Methods Initially, 1,232,492 echocardiography reports from 12 hospitals were identified from 1 January 2000 to 22 November 2022, and previously validated natural language processing modules were then applied to identify aortic gradients, LVEF, and presence of LVH. These reports were linked to mortality data, key comorbidities with a 2-year lookback covariate window, and date of any AVR. We then isolated echocardiograms demonstrating normal flow severe AS, LVEF ≥ 55% and LVH. Chart reviews were conducted to reduce missing data and outcomes were censored on the date of the chart review (October 4, 2023). To assess the association between AVR and mortality, Cox proportional hazards models considering treatment status (ie, AVR or not) were used with the index echocardiogram as time zero. Covariates used in risk-adjustment were chosen a priori based on conditions and laboratory values used in cardiac surgery mortality risk-adjustment, since those variables could plausibly confound the treatment decision. To address immortal time bias, AVR was considered a time-varying covariate. Multiple additional approaches with propensity scores were performed as sensitivity analyses. Results After application of inclusion and exclusion criteria, 4856 unique patients remained for analysis. Of those, 2043 (42.1%) received AVR with 841/2043 (41.2%) receiving surgical AVR and 1202/2043 (58.8%) receiving transcatheter AVR. Patients who received AVR had lower unadjusted mortality than those who did not receive AVR (33.6% vs. 47.1%, p &amp;lt; 0.001). After adjustment, and accounting for time-dependence of AVR, AVR was associated with reduced mortality (HR 0.81, 95% CI 0.73-0.89, p &amp;lt; 0.0001). The sensitivity analyses were all consistent with the primary analysis. Conclusions AVR was associated with reduced mortality for patients with severe AS, preserved LVEF, and LVH. This association persisted even after accounting for time-dependence, which tends to reduce the observed effectiveness of procedures in observational data. With over a million echocardiograms over more than 20 years, this is the largest known analysis of AVR outcomes in individuals with severe AS and LVH. Our findings suggest LVH may be a high-risk phenotype of individuals with AS, similar to dropping LVEF. As such, these results raise the potential of more proactive AVR clinical guidelines in individuals with LVH, even when LVEF is normal.Survival in AVR Vs No AVR

Differentiation of severe from non-severe mitral stenosis with dimensionless index and its prognostic implications in patients with rheumatic mitral stenosis

Abstract Introduction Accurate identification of the severity of rheumatic mitral stenosis (MS) commonly relies on measurement of mitral valve area (MVA) by transthoracic echocardiography (TTE). The dimensionless index (DI) of mitral valve (MV) was recently shown to be useful in identifying severity of degenerative MS. It is uncertain if DI MV is useful in rheumatic MS. Purpose We aimed to validate the DI MV in rheumatic mitral stenosis, identify threshold values of the DI MV for the accurate identification of severe and non-severe rheumatic MS, and study its association with clinically significant outcomes. Methods We studied DI MV in 406 cases of rheumatic MS, with 174 cases in a derivation cohort , 121 cases in a TTE validation cohort, and 111 cases in a transoesophageal echocardiography (TEE) validation cohort. Outcome data were collected in the derivation and TTE validation cohorts. DI MV was calculated by dividing the left ventricular outflow tract pulsed-wave Doppler time-velocity integral (TVI) by the MV continuous-wave Doppler TVI. Results In the derivation cohort, ROC analysis showed that MV DI was significantly associated with MS severity (AUC = 0.838, 95% CI, 0.780-0.897, p&amp;lt;0.001) but no threshold value was able to identify severe MS (MVA ≤ 1.5 cm2) with both sensitivity and specificity greater than 80%. DI MV ≤ 0.34 had the best combination of sensitivity and specificity (78.5% and 75.8% respectively). However, with an approach using two threshold values, namely DI MV ≤ 0.25 to identify severe MS and DI MV ≥ 0.40 to identify non-severe MS, both values showed a high specificity of 93.7%. When tested in the validation cohorts, these values have similar high specificity for identifying severe (93.8%) and non severe MS (91.4%). DI MV was univariately significant (HR = 0.075, 95% CI 0.0215-0.378, p=0.002) in Cox regression analysis for a composite outcome of death and MV intervention. Multivariate analysis incorporating age, sex, DI MV, pulmonary artery systolic pressure (PASP) and left ventricular ejection fraction (LVEF) showed that age, DI MV and PASP were independently associated with the composite outcome. Conclusion While not a replacement for MVA in the assessment of MS severity, the DI MV can rule-in or rule-out severe MS with a high specificity and is useful as a complementary tool in the integrative assessment of MS severity. DI MV is independently associated with composite outcomes of death and MV intervention.Receiver operating characteristic curveSensitivity and Specificity of DI MV

Outcomes of implantable cardioverter-defibrillators in patients with a left ventricular assist device: a systematic review and meta-analysis

Abstract Introduction Implantable Cardioverter-Defibrillators (ICDs) improve survival in advanced heart failure with reduced ejection fraction (HFrEF) and prevent sudden cardiac death. However, the prognostic benefits of ICDs among patients with a Left Ventricular Assist Device (LVAD) remain uncertain and controversial. Therefore, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of ICD implantation among LVAD recipients. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the peer-reviewed articles published in English assessing the impact of ICD implantation among LVAD recipients, till 10/01/2024. ICD implantation was defined as implantation before LVAD, simultaneous implantation with LVAD, or within 30 days of LVAD insertion. Two independent review authors assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data in forest plots. The primary outcome was all-cause mortality associated with ICD implantation compared to no ICD implantation, and the secondary outcomes included ventricular arrhythmia (VT), and hemorrhagic stroke. Heterogeneity was assessed using Q test and I2, with I2 &amp;gt; 50% indicating marked heterogeneity. Results A total of 13 observational studies comprising 54571 recipients of LVAD were included in the analysis of the primary outcome. All-cause mortality was similar among patients with ICD versus no ICD (Odds Ratio [OR]= 0.77; 95% CI, 0.57-1.04, I2= 89%, P=0.09), as shown in Figure 1. Likewise, ICD implantation was associated with similar rates of VT and hemorrhagic stroke (VT: OR= 1.81, 95% Cl, 0.82-4.01, I2= 90%, P=0.14; hemorrhagic stroke: OR= 1.01, 95% Cl, 0.81-1.25, I2= 0%, P= 0.95). Conclusion Among patients with HFrEF and LVAD as advanced heart failure therapy, ICD implantation didn’t provide additional prognostic survival benefit, suggesting possible use of LVAD without ICD implantation.Figure 1.Forest plot of mortality

Evaluation of concordance and association with clinical outcomes across eGFR values calculated with eight different formulas in a large cohort of european patients with atrial fibrillation

Abstract Background In randomized clinical trials of Direct Oral Anticoagulants (DOACs), the assessment of renal function impairment glomerular filtration rate (eGFR) in patients with Atrial Fibrillation (AF) has predominantly utilized the Cockroft-Gault (CG) formula for estimating Creatinine clearance (CrCl). However, in clinical practice, several other formulas for estimating glomerular filtration rate (eGFR) are employed. Limited data exist regarding the evaluation and comparison of eGFR/CrCl in AF patients. Objectives This study aimed to assess the concordance in the categorisation of renal function in in 6 classes taking into account eight different formulas for eGFR/CrCl (CG, CKD-EPI, CG/body surface area [BSA], BIS1, LMK, EKFC, FAS, MDRD) and their associations with a composite outcome (Major Adverse Cardiovascular Events [MACE] and all-cause death) in AF patients. Methods A contemporary European AF patient registry was utilized, and eGFR/CrCl were calculated using CG, CKD-EPI, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. eGFR was categorized according to KDIGO classes, with CKD patients defined as having eGFR/CrCl &amp;lt;60 ml/min/m2. Concordance was estimated using weighted Cohen’s kappa. Associations were evaluated through adjusted Cox regression analyses for the composite outcome, and results were plotted as spline curves. Results: A total of 8516 patients were included in the analysis (Median [IQR] age: 70 [63-77] years; 3518 women, 41.3%). Among the formulas, EKFC exhibited the highest median values of eGFR and the lowest prevalence of CKD patients, while BIS1 had the lowest median eGFR values, and the FAS formula led to the highest prevalence of CKD patients [Figure 1]. In the concordance analysis, CKD-EPI demonstrated the highest concordance with all other formulas, even if Cohen’s kappa for measuring the degree of concordance ranged from 0.61 to 0.88 [Figure 1]. In adjusted Cox regression analyses, all formulas were associated with an increased risk for the composite outcome, progressively as eGFR decreased. When plotted as spline curves, the associations with the composite outcome visually showed a similar behaviour of risks across eGFR values in all formulas compared to the CG spline [Figure 2]. Conclusions Among AF patients, the CKD-EPI formula exhibited variable, but substantially good concordance with CG, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. All calculated eGFR values showed a strong association with the composite outcomes, similarly to the CG formula, with higher risk when renal function decreased.FIGURE 1FIGURE 2

Does PhenoAge acceleration impact adverse outcomes following major surgery (rehospitalization or death)? A genome-wide association study and mendelian randomisation

Abstract Background Biological aging reflects the state of an individual's cellular and molecular function, and is distinct from chronological age; which reflects the passage of time[1]. Validated measures of biological aging, such as Phenotypic aging (PhenoAge) estimated from nine routine clinical biomarkers, have been associated with increased risk of age-related diseases and mortality in cohort studies[2]. However, the potential causal relationship between them remains unclear. In this study, we aim to identify genetic variants associated with PhenoAge Acceleration (PhenoAgeAccl) and adverse outcome after surgery (rehospitalisation or death within 365-days] and assess the causal relationship between these two phenotypes using Mendelian Randomization framework. Objectives -Perform a genome-wide association study(GWAS) on adverse outcomes following major surgery. -Assess the potential causal relationship between PhenoAgeAccl and adverse outcomes following major surgery using Mendelian randomization analysis. Methods We conducted a GWAS via plink using participants from the UKBiobank (Application 77596) to generate summary statistics for 6509 participants who had undergone major surgery within 365 days of their baseline assessment date(3). For quality control, SNPs were excluded if they didn't meet the following criteria: (1) imputation information score &amp;lt;0.3 (2) minor allele frequency &amp;lt;1%, (3) Hardy–Weinberg equilibrium test p-value significant at the Bonferroni-corrected level. Summary statistics for PhenoAgeAccl was obtained from a previous GWAS of European descents[4]. Gene enrichment analysis was performed using Multi-marker Analysis of GenoMic Annotation (MAGMA) in Functional Mapping and Annotation (FUMA). Then, genetic instruments for PhenoAgeAccl and adverse outcomes following surgery were identified to conduct a summary-based Mendelian Randomisation [Assumptions are listed in Figure 1]. Results GWAS for adverse outcomes following major surgery identified 3 lead SNPs (rs1360618, rs11848297, rs7978) [Figure 2]. Gene-set analysis showed enrichment in the immune system, cell migration, fear response, and iron metabolism. For PhenoAge Acceleration, gene-set analysis showed enrichment in immune system, and cell signalling pathways. 17 SNPs were selected which were used for the Two-Sample MR. We found no causal relationship, as the beta coefficient for Inverse variance weighted was -0.308 [standard error - 0.075, p=0.68]. For every 5-year increase in PhenoAge compared to chronological age, the risk of emergency re-hospitalisation or death increased by 21% (HR 1.16 – 1.3, p &amp;lt; 0.001). Conclusion Gene-set analysis for adverse outcomes following major surgery showed enrichment in immune system, iron metabolism, and fear response which have all recently been associated with mortality post-surgery in cohort studies(4,5). No causal relationship between PhenoAgeAccel and mortality post-surgery was established.Mendelian Randomisation assumptionsManhattan plot adverse-outcomes post-sur

Integrated care using the ABC-stroke pathway improves cardiovascular outcomes and survival in patients with recent ischaemic stroke: a population-based cohort study

Abstract Background A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed the ABC-stroke pathway, a holistic and integrated care approach to optimise the post-stroke management for patients with recent stroke, and associated heart disease. The ABC-stroke pathway is based on 3 pillars: "A" Appropriate Antithrombotic therapy; "B" Better functional and psychological status; and "C" Cardiovascular risk factors and Comorbidity optimisation (including lifestyle changes). There are limited data on the impact of adherence to the ABC-stroke pathway on post-stroke patient outcomes. Purpose We aimed to investigate the potential impact of ABC-stroke pathway adherence in the Clinical Data Analysis and Reporting System (CDARS) database in Hong Kong. Methods The analysis included patients with new-onset ischaemic stroke recorded in CDARS between 1st June 2006 and 31st May 2022. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between adherence to the ABC-stroke pathway and the primary outcome. The primary endpoint was a composite outcome of recurrent ischaemic stroke, transient ischaemic attack, haemorrhagic stroke, myocardial infarction, heart failure and all-cause death. Secondary outcomes were the individual components of the composite outcome, and cardiovascular death. Results Of the 9,669 included patients with ischaemic stroke (mean age 69.6 ± 13.4 years; 42.5% female), 58.1% were adherent to all 3 main ABC-stroke pillars. After 1 year of follow-up, adherence to the ABC-stroke pathway was associated with a lower risk of the primary composite endpoint (HR: 0.80; 95% CI: 0.72–0.88). Risk reductions increased progressively with a higher number of ABC-stroke criteria obtained (Figure 1). On multivariate analyses of the secondary outcomes, ABC-stroke pathway-adherent care was associated with a reduced risk of all-cause mortality (HR: 0.72; 95% CI: 0.62–0.85), cardiovascular death (SHR: 0.64; 95% CI: 0.45–0.90), haemorrhagic stroke (SHR: 0.50; 95% CI: 0.38–0.67) and heart failure (SHR: 0.771; 95% CI: 0.596-0.998) (Table 1). Conclusion In a large cohort of patients with ischaemic stroke, adherence to the ABC-stroke pathway was associated with a reduction of the risk of adverse outcomes.

Prevention of dementia using mobile phone applications (PRODEMOS): a multinational randomised controlled effectiveness-implementation trial

Abstract Background The expected increase of dementia prevalence in the coming decades will mainly be within low-and middle-income countries and those with low socioeconomic status (SES) in high income countries. Forty percent of dementia is associated with modifiable, lifestyle-related cardiovascular risk factors. Mobile health interventions with remote coaching can help reach underserved high-risk populations globally. Methods This open label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in persons aged 55-75 years of low SES in UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in CAIDE dementia risk score (including age, education, sex, systolic blood pressure, total cholesterol, BMI, physical exercise) after 12-18 months of intervention. Main implementation outcomes were coverage, acceptability, appropriateness, adoption, feasibility, sustainability, fidelity, and costs using a mixed methods approach. Findings Between 15th January 2021 and 18th April 2023, 1,488 persons were included and randomised (734 intervention, 754 control), with 1,229 (82·6%) available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months, the mean CAIDE score improved by 0·16 points in the intervention group vs. 0·01 in the control group (Mean Difference (MD) 0·16, 95% Confidence Interval (CI) 0·03-0·29). The effect was larger in those who adhered to the intervention (MD 0·27, 95%CI 0·12-0·44) and those planning to change lifestyle (MD 0·33, 95%CI 0·10-0·57). Ten percent of those invited participated; of these, 81% adopted the intervention and 50% continued active participation throughout the study. For the individual components of the CAIDE score, there were no statistically significant differences for systolic blood pressure, total cholesterol and BMI, but in the intervention group physical inactivity was reduced more than in the control group (MD 6·7%, 95%CI 2·1 to 11·2) and more participants quit smoking (MD -3·1%, 95%CI -4·8 to -1·5). Interpretation A coach-supported mHealth intervention to improve lifestyle is modestly effective in reducing dementia risk factors in those with low SES in the UK and any SES in China. Implementation is challenging in these populations, but those reached actively participated. Whether this will result in less cognitive decline and dementia requires a larger RCT with long follow-up.