Higher Baseline Research Articles

Predictors of the effectiveness to first-line CTLA4-Ig in patients with rheumatoid arthritis: the FIRST registry.

This study aimed to elucidate which bio-naïve patients with rheumatoid arthritis (RA) are suitable for treatment with CTLA4-Ig. This study enrolled 953 patients with RA who were administered their first biological disease-modifying antirheumatic drug (CTLA4-Ig, n = 328; tumour necrosis factor inhibitor [TNFi], n = 625) from July 2013 to August 2022. The primary outcome was the Clinical Disease Activity Index (CDAI) remission rate at week 24 in each group, adjusted using Propensity Score-based Inverse Probability of Treatment Weighting (PS-IPTW). After minimizing selection bias using PS-IPTW, the CDAI remission showed no significant difference between the CTLA4-Ig and TNFi groups (p= 0.464). Multivariable logistic regression analysis identified low baseline Health Assessment Questionnaire-Disability Index (HAQ-DI) scores as a contributing factor to the CDAI remission rate at week 24 in both groups, along with high baseline anti-citrullinated peptide antibody (ACPA) levels in the CTLA4-Ig group. However, among patients with high baseline HAQ-DI scores and low baseline ACPA levels (≦57.2), the CDAI remission rate was significantly higher in the TNFi group (29.8%) compared with the CTLA4-Ig group (5.9%, p< 0.0001). Among patients with high baseline HAQ-DI scores and ACPA levels (>57.2), the CDAI remission rate was significantly higher in the CTLA4-Ig group (35.6%) compared with the TNFi group (22.1%, p= 0.0057). Bio-naive RA patients with low HAQ-DI scores showed high treatment efficacy with no significant difference between CTLA4-Ig and TNFi. Among patients with high baseline HAQ-DI scores, TNFi and CTLA4-Ig were more likely to be effective in those with lower and higher baseline ACPA levels, respectively.

Interventions to Reduce Imaging in Children With Minor Traumatic Head Injury: A Systematic Review.

Reducing unnecessary imaging in emergency departments (EDs) for children with minor traumatic brain injuries (mTBIs) has been encouraged. Our objective was to systematically review the effectiveness of interventions to decrease imaging in this population. Eight electronic databases and the gray literature were searched. Comparative studies assessing ED interventions to reduce imaging in children with mTBIs were eligible. Two independent reviewers screened studies, completed a quality assessment, and extracted data. The median of relative risks with interquartile range (IQR) are reported. A multivariable metaregression identified predictors of relative change in imaging. Twenty-eight studies were included, and most (79%) used before-after designs. The Pediatric Emergency Care Applied Research Network (PECARN) rule was the most common intervention (71%); most studies (75%) used multifaceted interventions (median components: 3; IQR: 1.75 to 4). Before-after studies assessing multi-faceted PECARN interventions reported decreased computed tomography (CT) head imaging (relative risk = 0.73; IQR: 0.60 to 0.89). Higher baseline imagine (P < .001) and additional intervention components (P = .008) were associated with larger imaging decreases. The limitations of this study include the inconsistent reporting of important outcomes and that the results are based on non-randomized studies. Implementing interventions in EDs with high baseline CT ordering using complex interventions was more likely to reduce head imaging in children with mTBIs. Including the PECARN decision rule in the intervention strategy decreased orders by a median of 27%. Further research could provide insight into which specific factors influence successful implementation and sustained effects.

Variability of relative treatment effect among populations with low, moderate and high control group event rates: a meta-epidemiological study

BackgroundThe current practice in guideline development is to use the control group event rate (CR) as a surrogate of baseline risk and to assume portability of the relative treatment effect across populations with low, moderate and high baseline risk. We sought to emulate this practice in a very large sample of meta-analyses.MethodsWe retrieved data from all meta-analyses published in the Cochrane Database of Systematic Reviews (2003–2020) that evaluated a binary outcome, reported 2 × 2 data for each individual study and included at least 4 studies. We excluded studies with no events. We conducted meta-analyses with odds ratios and relative risks and performed subgroup analyses based on tertiles of CR. In sensitivity analyses, we evaluated the use of total event rate (TR) instead of CR and using quartiles instead of tertiles.ResultsThe analysis included 2,531 systematic reviews (27,692 meta-analyses, 226,975 studies, 25,669,783 patients).The percentages of meta-analyses with statistically significant interaction (P < 0.05) based on CR tertile or quartile ranged 12–18% across various sensitivity analyses. This percentage increased as the number of studies or range of CR per meta-analysis increased, reflecting increased power of the subgroup test. The percentages of meta-analyses with statistically significant interaction (P < 0.05) with TR quantiles were lower than those with CR but remained higher than expected by chance.ConclusionThis analysis suggests that when CR or TR are used as surrogates for baseline risk, relative treatment effects may not be portable across populations with varying baseline risks in many meta-analyses. Categroization of the continuous CR variable and not addressing measurement error limit inferences from such analyses and imply that CR is an undesirable source for baseline risk. Guideline developers and decision-makers should be provided with relative and absolute treatment effects that are conditioned on the baseline risk or derived from studies with similar baseline risk to their target populations.

The Role of Interleukin-8 in the Estimation of Responsiveness to Steps 1 and 2 of Periodontal Therapy.

To investigate the association between interleukin-8 (IL-8) levels in gingival crevicular fluid (GCF) and total oral fluid (TOF) and the responsiveness to steps 1 and 2 of periodontal therapy. One-hundred and fifty-nine patients affected by periodontitis received steps 1 and 2 of periodontal therapy. At baseline, TOF and GCF samples were collected and analysed for IL-8 (Il-8TOF/IL-8GCF) using flow cytometry. Therapy outcomes were relative proportions of residual periodontal pockets (PPD%), pocket closure (PC) rates and pocket probing depth (PPD) reductions; these were associated with IL-8TOF/IL-8GCF. High IL-8TOF was significantly associated with higher residual PPD% (p = 0.044) and lower PPD reduction compared to low IL-8TOF (high 0.79 ± 1.20 mm vs. low 1.20 ± 1.20 mm, p < 0.001) in non-smokers, while in smokers high IL-8GCF was related to lower PPD reduction (high 0.62 ± 1.22 mm vs. low 0.84 ± 1.12 mm, p = 0.009). Furthermore, high baseline IL-8TOF was significantly associated with poorer PC rates compared to medium and low concentrations in both non-smokers (high 41% vs. medium 55% vs. low 58%, p < 0.001) and smokers (high 34% vs. medium 44% vs. low 46%, p < 0.001). High IL-8 concentrations at baseline had a significant impact on residual PPD%, PC rates and PPD reduction. The findings suggest that, especially in non-smokers, baseline IL-8 levels collected from the TOF could serve as a component in the estimation of responsiveness to steps 1 and 2 of periodontal therapy.

Findings from the Mighty Girls Efficacy Trial: Changes in Acceptance of Dating Violence

Background/Objectives: Test efficacy of the social emotional learning (SEL)-based Mighty Girls program, a program culturally tailored for English-speaking Hispanic/Latino girls in seventh grade comprised of classroom sessions and a virtual reality computer game. We hypothesized that the curriculum would decrease risky sexual behaviors in a program that can be used as part of a comprehensive sex education curriculum or as a stand-alone program. Methods: A randomized group trial was conducted in which 22 low-income, predominately Hispanic schools within the Miami-Dade County Public School System were randomly assigned to intervention (consented n = 335) and control (consented n = 217) conditions. All study activities occurred after school. Primary outcome measures were resistance self-efficacy, acceptance of dating violence, sexual intentions, and sexual behavior. Assessments occurred at baseline, immediately post-intervention, 3-, 12-, and 24-months post-intervention. Changes in outcomes from baseline to 24 months were modeled using multi-level models to account for nesting of students within schools with full information maximum likelihood to account for missing data and baseline school attendance and enrollment in free and reduced lunch as covariates. Analyses are also controlled for multiple testing. Results: The program had a significant effect on reducing acceptance of dating violence at 24 months post-intervention (estimate = −0.083, p ≤ 0.05), but no effect on resistance self-efficacy, sexual intentions, or sexual behavior (p ≥ 0.58). Conclusion: Study findings demonstrate that a social emotional learning (SEL) curriculum can impact sexual behaviors such as susceptibility to dating violence. Low baseline levels for sexual intentions and behaviors as well as a high baseline of efficacy may have impacted findings for the other outcomes.

Basic self-disturbance in adolescents at risk of psychosis: temporal stability investigated by the experience sampling method in a mixed method study.

Basic self-disturbance (BSD), also called anomalous self-experiences (ASEs), are core phenotypic markers for schizophrenia spectrum disorders and a prepsychotic vulnerability marker considered to be temporally stable (trait-phenomenon). Studies of BSD in children and adolescents are lacking. To be clinically useful, we need to know more about the characteristics and temporal development of BSD in prepsychotic phases. This study used a smartphone application measuring the occurrence and subjective intensity of ASEs in the daily life of 27 help-seeking adolescents (12-18 years) repeatedly over a period of 6 months. A total of 5223 unique application-reports based on individually selected and verbatim descriptions of personal core ASEs were analysed by mixed methods. The intensity of ASEs, within subjects and between subjects and irrespective of time intervals or baseline scores obtained by the Examination of Anomalous Self-Experience (EASE) were relatively stable with a mean variability of 1.25 (0.4) SD. Participants with low EASE total scores at baseline had a significantly lower score on ASE intensity than those with high baseline EASE total scores at baseline (mean 2.42 vs 3.42, p=0.046). In this study, ASEs were not reported as essentially fluctuating experiences but as almost constantly present, demonstrating BSD as a mainly trait phenomenon in prepsychotic phases in persons under the age of 18. Considering the continuous experience of BSD and its predictive value for psychosis development, ASEs should be targeted and monitored to the same extent as other prepsychotic features.

Client characteristics and early working alliance development: A person-centered research approach

Objective Certain client characteristics are associated with early working alliance difficulties in psychotherapy. However, there is limited quantitative evidence on whether combinations of these characteristics (e.g., intersectional identities, prior treatment experiences) are related to alliance development. The present study leveraged a person-centered research approach to examine profiles of early alliance development and differences in the latent class structure of client characteristics among alliance development profiles. Method Individual psychotherapy clients (N = 2,579) rated the working alliance for their first four sessions and self-reported demographics, treatment history, and psychological distress. Therapists provided their assessment of clients’ primary presenting concerns at baseline. Results Latent profile analysis revealed three profiles of working alliance development: high and stable, moderate and increasing, and low and stable. Follow-up person-centered analyses (multigroup confirmatory latent class analysis) indicated that clients in the alliance profiles differed in their combinations of clinical and demographic characteristics. For example, women of color with high baseline distress and a history of prior psychotherapy were over-represented in the low and stable alliance profile. Conclusion These results are consistent with recommendations to holistically consider how clients’ characteristics and experiences shape psychotherapy processes. Results also highlight the utility of person-centered quantitative methods in psychotherapy research.

Factors involved in gastroesophageal varix-related events in patients with hepatitisC virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy.

The incidence of and factors involved in gastroesophageal varix-related events in hepatitisC virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear. We conducted a multicenter study using prospective data from 478 hepatitisC virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix. The median age was 70years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p<0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p=0.120). Across 35.7months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p=0.001). In the multivariate analysis, high-risk varix (p<0.001), high baseline gamma-glutamyl transpeptidase levels (p<0.001), and virologic failure (p=0.004) were significantly involved in varix-related events. The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

Long-term follow-up of the TRED-HF trial

Abstract Background The TRED-HF trial (1) found that 44% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after withdrawal of medical therapy. The longer-term risk of relapse is uncertain. Purpose This follow-up aims to investigate the longer-term risk of relapse in patients with recovered DCM and any possible predictive factors. Methods TRED-HF trial participants were followed until May 2023. The primary outcome was DCM relapse defined as &amp;gt;10% reduction in left ventricular (LV) ejection fraction to &amp;lt;50%, doubling in N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) to &amp;gt;400ng/L, or clinical recurrence of heart failure (HF). Therapy intensity for HF was calculated using QUAD scores. The incidence of relapse was calculated using Kaplan-Meier estimates. Predictors of relapse were investigated using Cox proportional hazard modelling. Results For all fifty-one patients, median follow-up from enrolment was 6 (IQR: 6-7) years. Overall, thirty-three patients (65%) relapsed with an estimated 5-year relapse rate of 61% (95% CI 45-73). Twenty patients relapsed during the randomised trial, nine of whom had a recurrent relapse during follow-up (Figure 1). Thirteen patients relapsed for the first time after completion of the trial; of those, one patient did not have therapy withdrawn during the trial, 8 had restarted low intensity HF therapy and 4 patients stayed on no therapy. Five patients stayed off HF therapy and did not relapse. The overall mean intensity of HF therapy was lower after the trial compared to enrolment (mean difference in QUAD score -6 [-8 to -4]; p&amp;lt;0.001). A mean reduction in medication intensity was also seen at the point of relapse during the trial and during follow-up (Figure 2). Of relapses during follow-up, seven had identifiable triggers (arrhythmia (n=4), pregnancy (n=1), hypertension (n=1), infection (n=1)). Patients taking more HF medications at baseline or with higher baseline NT-pro-BNP were more likely to relapse. Corrected atrial fibrillation was associated with reduced future risk of relapse. Conclusions In patients with recovered DCM, the risk of relapse after therapy withdrawal increased with longer follow-up. Lower doses of HF medications and recurrent external triggers contributed to relapse. Few patients who stopped medications had sustained remission. Recovery of DCM after correction of AF was associated with a low risk of relapse provided atrial fibrillation did not recur.

Sex differences in atherogenic lipid profile following acute coronary syndrome

Abstract Background Despite significant advancements in lipid-lowering therapy, the management of dyslipidemia remains challenging in patients with acute coronary syndrome (ACS). Significant differences are shown in lipid panels and management between different sexes following ACS. Objective To shed light on the alterations and characteristics of atherogenic lipoproteins and the characteristics of patients who achieve LDL-C targets after statin treatment, harnessing real-world data from electronic health records of patients with ACS after their discharge between sexes. Methods The data in the present study were derived from the iHeart program sponsored by the Chinese Cardiovascular Association. Eligible patients with a diagnosis of ACS from January 2014 to December 2021 during hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed the control of atherogenic lipid profiles between sexes. The primary outcome was the achievement of the LDL-C target, defined as LDL-C &amp;lt;1.8 mmol/L. A multivariable logistic regression model was used to assess the associations between patient characteristics and LDL-C achievement. Results Between 2012 and 2021, 4861 patients (1299 [26.7%] women) were hospitalised with a primary diagnosis of ACS (49.2% STEMI, 13.8% NSTEMI, and 33.8% UA). The mean age was 64.9 (12.4) years. In contrast to a higher proportion of AMI in men, more prevalence of UA was observed in women. Women had more cardiovascular comorbidities than men and were more likely to receive lipid-lowering therapies, blood pressure-lowering therapies, glucose-lowering therapies, and antiplatelet medications at discharge. In both men and women, TC, TG, LDL-C, ApoB, and non-HDL-C levels significantly decreased within 12 months (P&amp;lt;0.05). Women had less reduction in atherogenic lipid profile than men. The rate of LDL-C &amp;lt;1.8 mmol/L was similar between sexes (14.3% vs16.1%; P=0.136) at baseline, whereas within 12 months after discharge, women had a much lower achievement rate of LDL-C target than men (34.6% vs 45.6%; P&amp;lt;0.001). The risk factors for non-achievement of the LDL-C target in men were revascularisation, history of MI, atrial fibrillation, newly diagnosed MI, and high baseline LDL-C levels. For women, the risk factor was hypertension and diabetes. Conclusion Substantial sex disparities were observed in the management of atherogenic lipids. Despite a higher likelihood of receiving guideline-recommended medical therapy at discharge, women had poorer lipid control compared to men, especially among those with NSTEMI.

A decade of follow-up: atrial fibrillation, pulmonary pressure, and the progression of tricuspid regurgitation

Abstract Background While Atrial fibrillation is considered a risk factor for tricuspid regurgitation (TR), prospective long term data in the field is lacking. This analysis aimed to identify risk factors of TR progression during a decade of follow up among patients with and without AF. Methods Patients with full echocardiographic and clinical follow of at least 5 years were included. Individuals presenting with significant TR at baseline were excluded. Patients were divided into two groups based on baseline diagnosis of AF, followed by stratification according to systolic pulmonary artery pressure (sPAP). The primary outcome was the occurrence of new significant TR (≥ Moderate). Results Study population included 15,957 patients with a median age of 63 (IQR: 54-72) of whom 6,068 (38%) were women and 1,837 (11.5%) had baseline AF. During a median follow-up period of 11 years (8.5 – 13.5), 1,191 (7.5%) patients developed significant TR. Compared with sinus rhythm, patients with AF were 4 and 2 times more likely to develop significant TR during follow up in a univariate and multivariate models, respectively (95% CI 3.66 - 4.68 and 1.98 – 2.56, p &amp;lt; 0.001 for both). Older age, female sex, chronic kidney disease (CKD), left heart disease (LHD) and impaired right ventricular (RV) function, rate control and permanent AF were all risk factors for TR progression. The association of baseline AF with TR during follow up was sPAP – dependent, such that among patients with normal sPAP AF associated risk was high while among patients with high baseline sPAP AF-associated risk was significantly lower (HR 2.87 vs. 1.77; p for interaction &amp;lt; 0.001). Competing risk analysis with death as competing event yielded consisted results. Conclusions Baseline AF is a strong and independent risk factor for TR development. This association is more pronounced among patients with normal pulmonary arterial pressures, emphasizing the need for focused research on preventing TR development in this population.

High serum levels of CXCL13 predict lower response to csDMARDs in both ACPA-positive and ACPA-negative early rheumatoid arthritis.

Increased circulating levels of CXCL13 reflect synovial production and indicate immune dysregulation in patients with rheumatoid arthritis (RA). Here we tested whether CXCL13 predicts response to first-line treatment with methotrexate (MTX) in patients with early RA, independently and in association with anti-citrullinated protein antibodies (ACPA) and IgM-rheumatoid factor (RF). A prospective cohort of 243 early RA patients undergoing treat-to-target with MTX was evaluated. CXCL13, ACPA and IgM-RF were determined on baseline sera. Short-term variations of CXCL13 were measured after 2 months. The association of high CXCL13 (≥100 pg/ml) with disease remission after 6 months and escalation to second-line therapies within year 2 was evaluated in the total population and in ACPA-subgroups separately. High levels of CXCL13 were found in 53.6% of ACPA-positive and 31.5% of ACPA-negative patients, with minimal association with disease activity and RF. Serum CXCL13 remained stable after 2 months. High baseline CXCL13 independently predicted failure to achieve remission and more frequent requirement of second-line treatment in ACPA-positive patients, with adjusted ORs in the range of 0.17-0.49 for remission and 6.75 for second-line treatment. In ACPA-negative patients with high CXCL13, remission occurred at the expense of higher doses of MTX, and levels of CXCL13 predicted MTX escalations with an adjusted OR (95% CI) of 2.69 (1.35-5.34). High serum levels of CXCL13 identify a subgroup of RA patients who are more refractory to first-line treatment with MTX. CXCL13 appears a promising biomarker of response to MTX in both ACPA-positive and -negative early RA.

The role of fibrosis and inflammation for response and outcome prediction in candidates to cardiac resynchronization therapy: is response the right answer?

Abstract Background Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome. Purpose Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT. Methods 86 consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. An echocardiographic reduction of LV end-systolic volume ≥15% was used to define a patient as responder to CRT. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years. Results 44% of patients experienced the primary outcome. the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 38.5 ng/ml, AUC: 0.63, p=0.03, (OR 7.13 [1.12;45.41], p=0.03), together with TAPSE&amp;gt;17.5 mm (OR 10.86 [3.15;37.44], p&amp;lt;0.001) significantly correlated with the structural response to CRT in several prediction models. Baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p&amp;lt;0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p&amp;lt;0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood (Table). At Kaplan-Meyer curve patients with both high baseline sST2 and Gal-3 had the lowest survival probability (Figure). Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p &amp;lt; 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome. Conclusion In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.

Efficacy of the ABC Pathway for Integrated Care Across Phenotypes of Patients with Atrial Fibrillation: A Latent-Class Analysis Report from the mAFA-II Clinical Trial

Abstract Background The mAFA-II cluster randomised trial demonstrated the efficacy of a mobile health-technology implemented ‘Atrial fibrillation Better Care’ (ABC) pathway (mAFA intervention) for integrated care management of patients with AF. Objective To evaluate the effect of mAFA intervention across phenotypes of patients with AF. Design We conducted a latent-class analysis (LCA) according to eight variables, including age and comorbidities. Participants The mAFA-II trial enrolled AF patients between June 2018 and August 2019 across 40 centres in China. Main Measures We evaluated the interaction between the groups identified through LCA, and the effect of mAFA intervention on the risk of the primary composite outcome of all-cause death, stroke/thromboembolism, and rehospitalisations. Results were expressed as adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). Key Results Across the 3324 patients included in the trial (mean age 68.5 ± 13.9 years, 38.0% females), we identified three phenotypes: (i) low morbidity phenotype (n = 1234, 37.1%), (ii) hypertensive/coronary artery disease (CAD) phenotype (n = 1534, 46.2%), and (iii) mixed morbidity phenotype (n = 556, 16.7%). The effect of mAFA intervention on the primary outcome appeared greater in the low morbidity phenotype (aHR, 0.08; 95% CI 0.02–0.33) compared to the hypertensive/CAD (aHR, 0.30; 95% CI 0.16–0.58) and the mixed morbidity phenotype (aHR, 0.68; 95% CI 0.37–1.24), with a statistically significant interaction (pint = 0.004). Conclusions In patients with AF, the ABC pathway improved prognosis across different comorbidity phenotypes, although with some differences in the magnitude of risk reduction. Patients with more complex phenotypes require further efforts to improve their outcomes, considering their high baseline risk of adverse events. Trial Registration WHO International Clinical Trials Registry Platform (ICTRP) Registration number: ChiCTR-OOC-17014138.

Association between autonomic dysfunction, 12-year mortality and 10-year incident cardiovascular disease

Abstract Background Standing from a supine position requires a co-ordinated response in peripheral and central haemodynamic signals to protect the brain and body from sudden drops in blood pressure (BP) and has previously been shown to be an important measure of neuro-cardiovascular health (1-3). Previous studies have found an association between BP and heart rate recovery (HRR) to standing with all-cause mortality, cardiovascular disease and other health outcomes (4-8). However, almost all of these studies have exclusively investigated the association of consensus-defined HR/BP phenotypes measured at specific timepoints during standing. Purpose We hypothesised that assessing information from the entire haemodynamic response to orthostasis - instead of discrete timepoints or consensus definitions - may uncover novel associations between BP/HR responses to active stand and neuro-cardiovascular health in older adults. This may afford better physiological understanding of the longitudinal relationships between the response to standing and both Cardiovascular Disease (CVD) and mortality. Methods We used functional Principal Components Analysis (FPCA) to examine the determinants of variability in the complete haemodynamic response to active stand and examine which components were related to mortality and incident CVD in &amp;gt;4500 community-dwelling adults aged 50+. Results Figure 1 shows the mean response curve according to mortality status and Figure 2 the mean curve for participants free of CVD at baseline who later have CVD vs those who remain CVD-free during 10 year follow-up. All-cause mortality was associated with functional principal components which discriminate higher baseline HR, blunted HR peak and impaired HRR up to ~25 seconds after standing. Components that discriminated high baseline and impaired recovery of SBP from the post-stand nadir to 60 seconds post stand were also associated with all-cause mortality. This association remained even after covariate adjustment. Interestingly, neither baseline SBP nor orthostatic hypotension (OH) were associated with mortality. Components which discriminate high baseline and blunted HR peak; elevated stroke volume index and impaired recovery of DBP from ~25 seconds post stand were associated with 10-year incident CVD. Conclusions To our knowledge this is the first study to incorporate data driven information over the entire trace of the haemodynamic response to standing to investigate associations with incident CVD and mortality. The fact that components which discriminated high BP and impaired recovery of BP were associated with 12-year mortality and 10-year incident CVD when traditional summary measures of OH and baseline BP were not; suggests that incorporating information across the entire response to standing allows for richer and more flexible associations with health outcomes to be uncovered and allows for a better understanding of the underlying physiology leading to such associations.Figure 1:Mean trace of Mortality StatusFigure 2:Mean Trace of CVD Status

Out-of-pocket costs for patients diagnosed with high-grade glioma and their carers

Abstract Background This study aimed to describe the out-of-pocket costs incurred by patients diagnosed with high-grade glioma and their carers in the standard care arm of the Care-IS trial in the six to eight months following their diagnosis. Methods Carers completed monthly cost surveys detailing the out-of-pocket costs incurred by patients and carers over a six-month period. Seventy carers reported out-of-pocket costs at baseline (within two months following patient diagnosis), and a maximum of 50% of participants reported costs in any subsequent month. Costs were adjusted to 2023 AUD and reported as medians with interquartile range. Demographic factors were assessed to determine if any were significantly associated with being in the first or fourth quartile of total out-of-pocket costs at baseline. Results Median monthly costs for patient-carer dyads were highest at baseline ($535(IQR:$170-$930)), and two months post-recruitment ($314 (IQR:$150-$772)). The largest contributors to patient-carer costs were patient health service use and patient medications. Patient and carer health service use and medication costs varied over time. The median health service use and medication out-of-pocket costs for patients and carers were mostly below $100 per month, however, there was large variance in the upper 75th percentile for these cost categories. No factors were significantly associated with higher baseline out-of-pocket costs. Conclusion A HGG diagnosis has a significant and sustained financial impact on people who are diagnosed and their carers. Patients experience significant additional costs relating to their diagnosis and travel to receive care, and their carers also continue to experience sustained costs whilst managing the additional tasks associated with informal caregiving.

Prognostic potential of standard laboratory parameters in patients with metastatic renal cell cancer receiving first-line immunotherapy

Through their involvement in cancer metabolism, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) reflect the tumor burden and thus could have a prognostic potential for patients treated with immune checkpoint inhibitors (CPI). Therefore, this study investigated the prognostic potential of these parameters in a real-world cohort of patients with metastatic renal cell cancer (mRCC) under first-line CPI-based therapy. The retrospective study cohort included 82 mRCC patients treated with CPI-based first-line therapy between 2019 and 2023. Progression-free survival (PFS), overall survival (OS) and response rates were evaluated according to baseline levels and early dynamic changes of ALAT, ASAT, GGT and LDH. Multivariate Cox proportional hazard regression models were generated to identify independent prognosticators for PFS and OS. High baseline levels and non-normalized kinetics of ALAT, ASAT, GGT and LDH were significantly associated with shorter PFS and OS (p < 0.05), which was also reflected by lower response rates. Combining the four parameters at baseline into a 4-Risk-Score resulted in an enhanced prognostic power, as indicated by a higher C-index of 0.693 for OS compared to the individual parameters (≤ 0.663). Patients with all four risk factors present showed the worst PFS and OS. Overall, baseline levels and early kinetics of the four parameters as well as the 4-Risk-Score were identified as independent prognosticators for PFS and OS by multivariate analysis. As standard laboratory parameters, ALAT, ASAT, GGT and LDH are cost-effective and could be easily used either alone or in combination for therapy monitoring of CPI-treated mRCC patients.

HBcrAg is associated with prognosis of hepatitis B virus-related hepatocellular carcinoma in patients after hepatectomy undergoing antiviral therapy.

Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.

Evaluation of functional measures and laboratory parameters to portend limitations of spinal mobility in patients with radiographic axial spondyloarthritis

Aim of the workTo specify clinical and laboratory parameters related to limited spinal mobility in radiographic axial spondyloarthritis (r-axSpA) patients. Patients and methodsThe study included 202 adult r-axSpA patients. Clinical characteristics, medications, investigations including serum C-reactive protein (CRP) and human leukocytic antigen-B27 positivity were noted. Lateral lumbar flexion (LLF), chest expansion (CE) and tragus-to-wall distance (TWD) were measured. Values <2.5 percentile in LLF, CE and TWD were noted as reduced mobility of lumbar, thoracic and cervical spine, respectively. ResultsThe median age of patients was 43 years, male:female was 3.7:1. The time to diagnosis was 7.5 (3–40) years and were followed-up for 7.2 (4–22) years. Disease duration and high baseline CRP (>10 mg/L) were critical risk factors for reduced spinal mobility (p = 0.001 and p < 0.01). The duration to impaired LLF was significantly shorter in smokers (n = 105) (10.3;0–30.5 years) vs non-smokers (15.2;4.5–35 years) (p = 0.001) and in those with positive family history (n = 50) (9.7;0–20 years) compared to those without (12.9;4–35 years) (p = 0.09). LLF, CE and TWD were impaired in 40 % vs 75 %, 10 % vs 55 % and 12 % vs 60 % of patients with symptom duration of 10 vs 30 years respectively. Those with delayed introduction of biologics had significantly more impaired LLF, CE and TWD: 10.1(2–25) vs 14(3–33) years; 10.4(3–26) vs 17.5(8–33) years; 10.7(3–27) vs 16.7(5–33) years; p = 0.001 for all, respectively). ConclusionsThe most prominent factors affecting spinal mobility were the duration of symptoms and high serum CRP levels. The decreased spinal mobility was markedly less in patients with the early introduction of biologic therapy.

Zero-Dollar Copayment Impact on Adherence Scores for Centers for Medicare and Medicaid Services Star Ratings Generic Medications.

The Centers for Medicare & Medicaid Services (CMS) Star Ratings system pushes Medicare Advantage health plans to achieve ever greater attainments in key metrics, including adherence to hydroxymethylglutaryl-CoA reductase inhibitor (statins), renin-angiotensin system (RAS) antagonist, and noninsulin antihyperglycemic (DM) medications. The purpose of this observational study was to evaluate the impact of expanding a $0 copayment (copay) benefit from mail order-only to mail order plus retail pharmacies on adherence to statin, RAS, and DM medications. Medicare beneficiaries with and without a $0 copay expansion who received ≥ 1 dispensing of a generic, CMS Star Ratings RAS, statin, and/or DM medication during both 2021 and 2022 were included. Outcomes included changes in proportion of days covered (PDC) from 2021 to 2022 and proportions of patients with a PDC ≥ 0.8 in 2022. Overall (N = 65,716), patients had a high ( > 0.930) mean baseline PDC. Patients with $0 copay expansion had a statistically significant greater mean PDC increase for statin (adjusted P = 0.038), reduction for RAS (adjusted P = 0.036), and no difference for DM (adjusted P = 0.696). Patients with a $0 copay expansion had statistically significant higher proportions of beneficiaries with a PDC ≥ 0.8 for statin (adjusted P = 0.003) and RAS (adjusted P = 0.003) but not DM (adjusted P = 0.256). An expanded $0 copay was associated with minor increased generic statin medication adherence. In populations with a high baseline PDC, expanding a $0 copay benefit on generic statin, RAS, and DM medications to dispensing outside of mail order may only contribute slightly to an increase or sustainment of a health plan's CMS Star Ratings.