Low Risk Profile Research Articles

Subtypes of mental health difficulties and levels of resilience in Spanish adolescents

Emotional and behavioral difficulties are common among adolescents, and the role of psychological resilience in mitigating their impact needs further investigation. This study aimed to examine profiles of mental health difficulties combined with resilience levels in 1,425 Spanish adolescents at-risk. The participants were 1425 adolescents (59.9% girls). Mental health profiles were determined using the Strengths and Difficulties Questionnaire and the Connor-Davidson Resilience Scale (CD-RISC-10) via Latent Profile Analysis and compared for sociodemographic variables and mental health associated variables. Five profiles emerged: Subclinical (16%), Externalizing Problems (19%), Internalizing Problems (22%), Low Risk (32.5%), and Well-Adjusted (10%). Females had higher risk. Well-Adjusted and Low-Risk profiles differed significantly in all variables. Well-Adjusted profile had the lowest distress and psychosocial difficulties, and the highest quality of life; while the Subclinical profile showed the opposite pattern. Identifying and validating risk groups for emotional and behavioral difficulties, considering resilience, enables interventions promoting emotional well-being and preventing mental health challenges.

ESG Factors, Returns and Volatility: A Tale From Brazilian Market Data

Objective: This study aims to investigate the relationship between Environmental, Social, and Governance (ESG) factors and financial market performance in Brazil. The objective is to understand the impact of ESG scores on firms’ returns and risk profiles, thereby informing investment strategies and policy decisions. Theoretical Framework: The research is grounded in theories of sustainable finance and risk management, with emphasis on how ESG integration can influence financial outcomes. Notable frameworks include Cochrane’s “factor zoo” and the role of investor attention and analyst coverage in mitigating crash risk. Method: Data for the study was obtained from the Refinitiv Eikon database, covering firm-level ESG characteristics and market data, such as returns and volatility. Ordinary least squares (OLS) regression was used to analyze cross-sectional data, exploring the relationship between ESG scores and financial performance metrics across various sectors. Results and Discussion: The results show no significant relationship between returns and ESG scores. However, a negative and statistically significant relationship was found between ESG scores and volatility, suggesting that firms with higher ESG ratings tend to exhibit lower risk. ESG Controversies Score (ECSC) displayed negative correlations with other ESG metrics, indicating that companies involved in controversies tend to have lower overall ESG scores. Research Implications: These findings suggest that while ESG scores may not directly influence returns, they play a role in risk management, highlighting the importance of ESG factors for investors seeking lower-risk profiles. Originality/Value: This research contributes to the understanding of ESG’s role in the Brazilian market, offering empirical evidence on how ESG integration can shape financial performance and risk, providing a nuanced view of ESG’s impact on investment decisions.

Comparison of 6 cycles of isatuximab with lenalidomide, bortezomib and dexamethasone (I-VRd) versus 3 cycles of I-VRd followed by one cycle of high-dose melphalan in newly diagnosed low-risk multiple myeloma. Protocol for a multicenter, prospective, randomized, phase II clinical trial (ELIAS-Trial)

Newly diagnosed multiple myeloma patients who are eligible for transplant usually receive several induction cycles of therapy, followed by one or two cycles of high-dose melphalan and autologous stem cell transfusion. In myeloma patients, high-dose melphalan improves overall survival and progression-free survival. However, melphalan exposure increases the risk of secondary malignancies and may lead to the transformation of residual myeloma cells into more aggressive clones, which may accelerate relapse. It remains to be determined whether low-risk patients also derive additional benefit from high-dose melphalan therapy compared with less toxic regimens. Here we publish the study protocol of a multicenter, interventional, controlled, randomized, prospective and open-label phase II trial to investigate whether patients with a low-risk profile (R-ISS stage I, characterized by a low tumor burden and the absence of negative cytogenetic findings or elevated LDH levels) and a standard-risk gene expression profile (using the SKY92 GEP assay) can be sufficiently treated with intensified consolidation regimens without prior high-dose melphalan chemotherapy. The primary objective is to assess whether three cycles of isatuximab, bortezomib, lenalidomide and dexamethasone (I-VRd) followed by stem cell apheresis and three additional cycles of I-VRd will result in a non-inferior rate of complete remission (CR) combined with MRD-negativity at week 40 after the start of induction therapy compared to three cycles of I-VRd followed by standard of care treatment (such as stem cell apheresis, high-dose melphalan, and autologous stem cell transplantation). We hypothesize that this approach could reduce toxicity, cost of treatment and the likelihood of the development of a more malignant plasma cell clone, while improving overall survival (OS) and progression-free survival (PFS) in newly diagnosed low risk myeloma patients.EU Trial Number2022-500453-16-00, https://clinicaltrials.gov/study/NCT05665140, identifier NCT05665140. Registration Date: 21.07.2022.

Alexithymia and estimated 10-year cardiovascular disease risk in healthy adults: a community-based cross-sectional study.

This cohort study aimed to explore whether and to what extent alexithymia would be associated with cardiovascular disease (CVD) risk over an estimated 10-year period, over and above established clinical cofactors (i.e., depressive symptoms, quality of life, sociodemographic, anthropometric, lifestyle, and biological data), in a low-risk population of blood donors. A sample of 1,021 adult Italian blood donors (age 46.9 ± 8.39; 61.2% men) was consecutively recruited. The 10-year-CVD risk score was estimated using the CUORE risk score (CRS). Sociodemographic, lifestyle, anthropometric, biological, and psychological (i.e., quality of life, depressive symptoms, and alexithymia) CVD risk data were assessed using validated self-report measures or clinical records. As expected, most participants (78.5%) had a low CVD risk (CRS < 3%) and an overall low-risk profile for all the parameters. Compared with subjects at low risk of CVD (n = 911, 78.5%), those with high risk (i.e., rated ≥3 on CUORE risk assessment; n = 250, 21.5%) reported higher levels of alexithymia (p < 0.001). Subjects with higher alexithymia (n = 236, 23.1%) reported higher levels of psychosocial impairment, depressive symptoms, and biological risk variables for CVD. Alexithymia was significantly associated with 10-year CVD risk (OR = 1.02, 95% CI = 1.01-1.04, p = 0.009), even after adjusting for key sociodemographic and clinical risk variables. Although limited by the cross-sectional design, this study is the first to show that alexithymia leads to a higher risk for 10-year CVD estimate in healthy subjects with low-risk profile, regardless of known biomarkers and traditional CVD risk factors.

Colorectal Cancer Incidence and Mortality After Negative Colonoscopy Screening Results

The current recommendation for a 10-year rescreening interval after a negative colonoscopy screening (NCS) result has been questioned, with some studies showing a persistently lower risk of colorectal cancer (CRC) after NCS results. To examine long-term CRC incidence and mortality after NCS results (ie, no presence of CRC or polyps) and according to a risk score based on major demographic and lifestyle risk factors. In this cohort study, 3 prospective US population-based cohorts from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study were followed up from 1988 and 1991 to 2020. Data from the National Health and Nutrition Examination Survey (NHANES) from the January 1, 2017, to December 31, 2018, cycle were used to compare the risk profile distribution with that of the general US population. Data analysis was performed from October 2023 to August 2024. Time-varying status of NCS results and risk score. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs for incidence and mortality of CRC. A total of 195 453 participants (median [IQR] age, 44 [37-56] years at baseline; 81% female) were followed up for a median (IQR) of 12 (6-20) years. Among 81 151 individuals with NCS results and 114 302 without endoscopy, 394 and 2229 CRC cases and 167 and 637 CRC deaths, respectively, were documented. Negative colonoscopy screening results were consistently associated with lower CRC incidence (HR, 0.51; 95% CI, 0.44-0.58) and mortality (HR, 0.56; 95% CI, 0.46-0.70) for 20 years. Among individuals with NCS results, those with an intermediate risk (scores, 6-7) and low risk (scores, 0-5) did not reach the 10-year cumulative incidence of CRC (0.78%) of the high-risk individuals (scores, 8-12) until 16 and 25 years after initial screening, respectively. These findings provide evidence for shared decision-making between patients and physicians to consider extending the rescreening intervals after an NCS result beyond the currently recommended 10 years, particularly for individuals with a low-risk profile. These results showed, as a proof of concepts, the importance of considering known CRC risk factors when making decisions for colonoscopy rescreening.

BIOM-60. UNDERSTANDING THE INTERSECTION OF RACE, SEX, AND GENOMIC PROFILES IN MENINGIOMA PATHOPHYSIOLOGY

Abstract BACKGROUND While meningioma incidence and outcomes vary by sex and race, the potential underlying molecular differences possibly contributing to these disparities are less understood. Herein, we explore the clinical and genomic characteristics of meningiomas across groups characterized by age and sex. METHODS We analyzed adult patients with primary meningiomas resected from 2012 to 2023. Patients underwent whole exome sequencing, and demographic data were categorized into four groups based on self-reported race and sex, which included White females, White Males, Black females, and Black males. The primary analyses involved comparisons of tumor characteristics, socioeconomic status (median zip code income, % with high school diploma, health insurance status, distance from hospital), genomics, and recurrence rates. RESULTS The study included 509 primary meningiomas. White females exhibited low-risk genomic profiles characterized by driver mutations in KLF4 (+/- TRAF7) (p=0.010) and POLR2A (p=0.045), with no associated CNVs (p=0.410). This benign molecular profile correlated with lower WHO grades (p=0.013) and a lower incidence of recurrence (p=0.0003). Black females had meningiomas enriched with Hedgehog pathway mutations (p=0.0035) and a predilection for the anterior skull base (p=0.034), leading to an increased risk of recurrence (p=0.026). White males showed an aggressive genomic profile, including chromosome 1p loss (p=0.025) and 10q loss (p=0.067), associated with a high risk of recurrence (p=0.0002). Black males had meningiomas with chromosome 14q loss (p=0.0002), the highest incidence of high-grade meningiomas (p=0.048), and a 4.5-fold increased risk of recurrence (OR 4.5 [1.6-11.8]; p=0.006). Black males also experienced the worst progression-free survival (HR 5.5 [2.5-12.4]; p&amp;lt;0.0001), independent of WHO grade, extent of resection, and socioeconomic status. CONCLUSIONS Each demographic has a distinct molecular profile that correlates with clinical behavior in a race and sex-specific manner. Black males are disproportionately affected by biologically aggressive meningiomas, leading to higher tumor grade and recurrence rates.

Chronic Subdural Hematomas-A Retrospective Analysis of the Internal Architecture and Evaluation of Risk Factors for Recurrences After Surgical Therapy.

Background: Chronic subdural hematoma (CSDH) is increasingly common due to the aging population and widespread use of anticoagulant and antiplatelet medications. The objective of this study is to examine the internal composition of CSDH and explore potential risk factors associated with its recurrence. Methods: This retrospective study analyzed data from 189 patients who underwent surgery in our department between 2014 and 2018. Recorded data included demographics, clinical information, details of surgical interventions, computer tomography (CT) scans, neurological assessments, and follow-up data. The outcome was evaluated clinically and through CT follow-up conducted 4-12 weeks post-surgery. CT scans measured various parameters, including hematoma thickness, hyperdense regions, chronic components, and membrane presence. Results: Patients after the evacuation of CSDH were significantly more common males (66.1%, p > 0.001) had a significantly higher BMI (p < 0.001, 61.6%), arterial hypertension (p < 0.001, 68.3%), and the intake of anticoagulant therapy (p < 0.001, 58%). The recurrence rate was 18.6% after 4 weeks and 2.1% after 8-12 weeks. After uni- and multivariable analysis, the initial hemispheric type (p = 0.019, HR: 3.191; p = 0.012, HR: 3.810) and the increasing preoperative midline shift in CT (p = 0.028, HR: 1.114; p = 0.041, HR: 1.107) were found as independent predictors for recurrence. Overall, outcomes were favorable with a modified Rankin scale (mRS) of 0-2 at discharge (72%), after 4 (89.7%) and 12 (87%) weeks. Conclusion: According to our data, increasing midline shift before surgery and initial hemispheric type of hematoma were independent predictors of recurrence. Most patients achieved an excellent outcome with a low-risk profile.

Unraveling the paradox: the impact of one or more traditional risk factors on short-term mortality following acute coronary syndromes.

Abstract Background It has been recently suggested that individuals without exposure to any standardized modifiable risk factors may have an increased risk of all-cause mortality from acute coronary syndromes (ACS) compared with their counterparts with one or more risk factors, including diabetes. Purpose To estimate the individual contribution of the four traditional risk factors to the risk of adverse outcomes from first ACS. Methods We analyzed data from 70,953 Caucasian patients presenting with first ACS, but without prior coronary heart disease in the International Survey of Acute Coronary Syndromes (ISACS) Archives registry network from October 2005 to January 2021. The primary outcome was all-cause mortality within 30 days after hospital admission. We calculated sex-specific risk ratios (RRs) stratifying traditional risk factors, current smoking, diabetes, hypercholesterolemia and hypertension into mutually exclusive categories using a balancing strategy by inverse probability weighting. Results Compared with patients presenting without risk factors, those with diabetes had significantly higher 30-day mortality in both women (RR, 1.29; 95% CI, 1.06-1.57) and men (RR, 1.40; 95% CI, 1.16-1.69). By contrast, patients who were current smokers or presented with a history of hypercholesterolemia or hypertension had significantly lower 30-day mortality than patients with no risk factors with RRs ranging from 0.53; 95% CI 0.42–0.67 in women who were smokers to 0.46; 95% CI 0.37–0.59 in men with hypercholesterolemia. The impact of diabetes on mortality was obscured in patients who concomitantly presented with diabetes and one more traditional risk factor. The RRs in combination with current smoking were 1.39; 95% CI 0.92 -2.09 in women and 0.89; 95% CI 0.68 -1.17 in men; with hypercholesterolemia: 0.91; 95% CI 0.66 -1.25 in women and 0.75; 95% CI 0.53–1.06 in men; with hypertension: 1.14; 95% CI 0.99–1.32 in women and 1.12; 95% CI 0.96–1.31 in men. Conclusions Diabetes confers a significant independent excess mortality risk at 30 days following ACS. Dilution bias in this setting refers to the weakening of the observed effect of diabetes because of the inclusion of "one more" risk factor with lower risk profile. Potential misinterpretation of the relationship between diabetes and death from ACS may negatively affect healthcare organization

The importance of comorbidities in idiopathic and associated with connective tissue disease pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction Comorbidities play a major role in the prognosis of patients with pulmonary arterial hypertension (PAH). These comorbidities are present in more than 80% of patients diagnosed in the last years with idiopathic PAH (iPAH) and their presence is associated with increased morbidity and mortality although its influence on PAH associated with connective tissue disease (PAH-SSc) is unknown. We studied the impact of comorbidities on iPAH and PAH-SSc in the Spanish population. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classified into: no comorbidities, 1-2 comorbidities and ≥3 comorbidities. We analyzed the impact of comorbidities in baseline characteristics, exercise capacity and hemodynamic profile, as well as in the risk profile and initial treatment. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results 757 patients were selected for this study. The characteristics of the patients are shown in Table 1. As the number of comorbidities increases (0/1-2/≥3) we found higher age (49/59/67 years; p&amp;lt;0.001), higher percentage of male sex (12.9/29.9/43.4%; p&amp;lt;0.001) and higher FC III at diagnosis (42.7/46.9/59.6%; p=0.013). We observed a shorter distance in 6MWD, higher NT-proBNP levels, lower DLCO and a less unfavorable hemodynamic profile (PAPm, PAWP, CI and PVR). The most frequent comorbidities were a history of smoking (46.4%), followed by arterial hypertension (41.5%), obesity (24.6%) and chronic kidney disease (19.2%). Diabetes mellitus, although less frequent, reached more than 55% in patients with ≥3 comorbidities (p&amp;lt;0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p&amp;lt;0,001). Intermediate risk profile was the most common (58.4%) and this reached 68.7% in those with ≥3 comorbidities due to a lower number of patients in a low-risk profile (p&amp;lt;0.001). A statistically significant lower survival (p&amp;lt;0.001) was observed in patients with ≥ 3 comorbidities; however, we found no differences between 0 and 1-2 comorbidities at 7-year follow-up (Figure 1). Variables associated with mortality were male sex (HR 1.88, 95% CI 1,26 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06) and the presence of ≥3 comorbidities (HR 1.49, 95% CI 0.98 – 2.27), not the presence of connective tissue diseases, which were not associated with increased mortality in our study. Conclusions The presence of comorbidities in iPAH and PAH-SSc is very frequent in the Spanish population. They are associated with a worse clinical profile, risk profile, lower use of oral double theraphy and prostacyclins. The presence of ≥3 comorbidities is associated with worse survival, not the presence of 1-2 comorbidities or connective tissue disease.

Protein quantitative trait loci identifies genetic biomarkers of proteins associated with measures of myocardial fibrosis in new-onset, treatment naive rheumatoid arthritis

Abstract Introduction The excess risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) compared to the general population is attributed to chronic inflammation. Identifying the underlying mechanisms and shared inflammatory pathways more precisely would enable tailored treatment. Purpose To identify genetic variants associated with the cardio-metabolic-inflammatory proteomic signature in patients with early, treatment-naïve RA and low CVD risk. Methods The Coronary Artery Disease Evaluation in RA (CADERA) study was a bolt-on to a RCT of patients with early, treatment-naïve RA and low CVD risk profile (maximum of 1 traditional CVD risk factor and no diabetes mellitus). Normalised expression of 334 proteins from 75 CADERA patients who underwent cardiovascular magnetic resonance imaging (CMR) was measured using the Olink Proximity Extension Immunoassay across Inflammation, Cardiovascular II, III and Cardiometabolic panels. Genome-wide single nucleotide polymorphism (SNP) data were generated using the Illumina Global Screening Array and was imputed and checked for data quality using standard approaches. Proteins associated with CMR parameters were identified using Bayesian mixed effects linear regression. Protein quantitative trait locus (pQTL) analysis was then performed using linear regression models adjusted for age, gender, and systolic blood pressure. Cis-pQTLs were defined as SNPs within 1Mb of the protein-encoding gene, and significance threshold was set at 1e-5. Due to sample size, trans-pQTLs were not considered in this analysis. Linkage disequilibrium (LD) clumping was performed using PLINK software to identify index SNPs defined as the most significant variant in LD (r2 &amp;lt;0.5) within a region of +/- 250Kb. Results Following quality control 318 proteins and 5,971,781 SNPs were available for analysis in 75 CADERA patients. The median age was 51 years [inter-quartile range (IQR) 40 - 61] with 52/75 (69%) females, 40/75 (53%) current/ex-smokers, and median body mass index (BMI) 26.4kg/m2 (IQR 23.3 - 28). Participants had a median RA symptom duration of 21.9 weeks (IQR 14.4 - 32.7). Only 8/75 (10%) reported a history of hypertension, hypercholesteroaemia or family history of CVD. 54 out of 318 proteins were associated with CMR measures of myocardial fibrosis and/or vascular stiffness. 460 cis-pQTLs were identified for 20 out of the 318 proteins. LD clumping revealed 40 cis-pQTLs independently associated with these 20 proteins. Of these, NOTCH3 (rs34763630) was positively associated with extracellular volume, and SELPLG (rs7980427) was negatively associated with late gadolinium enhancement as detected on CMR (table 1). No other proteins with genetic support were associated with CMR measures. Conclusion This study for the first time, implicates genetic markers associated with two proteins as putative candidate biomarkers of CMR-identified myocardial fibrosis in new-onset RA that now warrant validation in an independent cohort.

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p&amp;lt;0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p&amp;lt;0-001), obesity (17.1 vs 20.7%; p&amp;lt;0.001) and diabetes (9.4 vs 22.1%; p&amp;lt;0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p&amp;lt;0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy

Objective: To investigate the interactions between select flavonoids (Luteolin, Quercetin, Apigenin, Kaempferol, and Amorphine) and the CXCR3 receptor, evaluating their potential as novel therapeutic agents in cancer immunotherapy. Methods: Molecular docking simulations were employed to analyze flavonoid-CXCR3 receptor interactions. Comprehensive in silico ADMET analyses were conducted to assess pharmacokinetic properties and toxicity profiles of the compounds. Results: Flavonoids exhibited high-affinity binding to the CXCR3 receptor, with binding affinities ranging from -8.7 to -13.0 kcal/mol. Amorphine demonstrated the highest binding affinity (-13.0 kcal/mol), indicating superior inhibition potential. Luteolin showed optimal ADME characteristics, including favorable oral bioavailability (62%) and blood-brain barrier permeability (log BB -1.911). Molecular docking analyses identified critical amino acid residues (TYR205, TYR308, TRP109, PHE131, and ASN132) in flavonoid-CXCR3 interactions. In silico toxicity predictions suggested low risk profiles for all examined flavonoids. Conclusion: This study provides evidence for the potential of flavonoids as CXCR3 receptor antagonists in cancer immunotherapy. The elucidated molecular interactions and favorable ADMET profiles warrant further investigation of these compounds. Future research should focus on optimization of flavonoid-based CXCR3 inhibitors, preclinical and clinical evaluations, and assessment of their immunomodulatory effects within the tumor microenvironment. These findings contribute to the development of novel, flavonoid-derived therapeutic strategies in cancer treatment.

Real-world evidence on pulmonary arterial hypertension: interim analysis from the Italian observational study INSPECTIO

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters

Making Sense of Topical Pain Relief Options: Comparing Topical Analgesics in Efficacy and Safety.

In patients with musculoskeletal (MSK) conditions, pain is the leading contributor to disability and significantly limits mobility and dexterity. This narrative review describes the efficacy and safety of topical analgesics in common use today. Secondary literature gained via a literature search using PubMed.gov and the Cochrane library were used. Recent literature (2000-2023) on several major classes of topical analgesics and topical delivery systems were reviewed to provide strength of recommendation taxonomy (SORT) levels. A total of 86 articles were reviewed. Level 2. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) and cabbage leaf wraps (CLW) appear to be best suited for multiple types of acute MSK pain, and topical nitroglycerin is helpful when used specifically for rotator cuff pain in patients seeking relief while performing activities of daily living and willing to treat for long periods of time. For compounded topical formulations, it may be better to offer single agent creams based on patient preferences. Little data support the use of cryotherapy. Traumeel could be a promising natural analgesic that compares with diclofenac. Topical lidocaine appears best suited for postherpetic neuropathic pain. O24 is a reasonable alternative with a low risk profile to treat pain in patients with fibromyalgia syndrome. Choice of topical agents should be guided by current evidence accounting for type of pain, medication side effects, patient comorbidities, as well as patient preference, convenience, and cost. Of the topical analgesics and modalities reviewed, SORT level A evidence was found for topical NSAID use in decreasing MSK pain, topical lidocaine for postherpetic neuralgia, and nitroglycerin patches for treating rotator cuff pain if used for prolonged periods of time. Alternative treatments such as CLW and Traumeel show promising results (SORT level B).

Basiliximab vs. No Induction Therapy in Kidney Transplant Recipients with a Low Immunological Risk Profile Receiving Tacrolimus/Mycophenolate/Steroids Maintenance Immunosuppression.

Background: Induction therapy with basiliximab is recommended in kidney transplant (KT) recipients with a low immunological risk (LIR) profile. Whether basiliximab is associated with a decreased risk of acute rejection (AR) and graft loss is controversial. Methods: In our institution, LIR patients (absence of anti-HLA antibodies before KT) are inducted with basiliximab in case of living-donor KT, while deceased-donor KT recipients receive no induction. Maintenance immunosuppression is similar, including a combination of tacrolimus (Tac), mycophenolate (MPA) and steroids. In this single-center retrospective study, we included all adult LIR patients who underwent KT between 1 January 2015 and 31 December 2022. Results: Of the 471 patients included, 354 received no induction and 117 received basiliximab. The median (IQR) number of HLA A-B-DR mismatches was 3 (2-3) and 2 (2-4) in the no induction group and the basiliximab group, respectively. The cumulative incidences in the no induction group vs. the basiliximab group of acute rejection and graft loss over 5 years post-KT were similar at 8.9% vs. 7.8% (p = 0.8) and 8.5% vs. 4.2% (p = 0.063), respectively. In multivariable Cox regression analysis, delayed graft function emerged as an independent risk factor for acute rejection (hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.23-6.13, p = 0.014) and graft loss (HR 9.32, CI 4.10-21.1, p < 0.001). Conclusions: Basiliximab did not provide any advantage in terms of rate of acute rejection and graft survival within 5 years post KT compared with a strategy without induction therapy in patients with a low immunological risk profile receiving triple maintenance immunosuppression Tac/MPA/steroids.

Prolonged Time-to-antihypertensive Therapy Worsens Organ Damage and Blood Pressure Control in Arterial Hypertension.

Delay in arterial hypertension (AH) diagnosis and late therapy initiation may affect progression towards hypertensive-mediated organ damage (HMOD) and blood pressure (BP) control. We aimed to assess the impact of time-to-therapy on BP control and HMOD in patients receiving AH diagnosis. We analysed data from the Campania Salute Network, a prospective registry of hypertensive patients (NCT02211365). At baseline visit, time-to-therapy was defined as the interval between the first occurrence of BP values exceeding guidelines-directed thresholds and therapy initiation; HMOD included left ventricular hypertrophy (LVH), carotid plaque, or chronic kidney disease. Optimal BP control was considered for average values < 140/90 mmHg. Low-risk profile was defined as grade I AH without additional cardiovascular risk factors. From 14,161 hypertensive patients, we selected 1,627 participants who were not on antihypertensive therapy. This population was divided into two groups based on the median time-to-therapy (≤ 2 years n = 1,009, > 2 years n = 618). Patients with a time-to-therapy > 2 years had higher risk of HMOD (adjusted odds ratio, aOR:1.51, 95%, CI:1.19-1.93, p < 0.001) due to increased risks of LVH (aOR:1.43, CI:1.12-1.82, p = 0.004), carotid plaques (aOR:1.29, CI:1.00-1.65, p = 0.047), and chronic kidney disease (aOR:1.68, CI:1.08-2.62, p = 0.022). Time-to-therapy > 2 years was significantly associated with uncontrolled BP values (aOR:1.49, CI:1.18-1.88, p < 0.001) and higher number of antihypertensive drugs (aOR:1.68, CI:1.36-2.08, p < 0.001) during follow-up. In low-risk subgroup, time-to-therapy > 2 years did not impact on BP control and number of drugs. In hypertensive patients, a time-to-therapy > 2 years is associated with HMOD and uncontrolled BP.

Recent advances in acupuncture for pain relief.

Acupuncture therapy has achieved global expansion and shown promise for health promotion and treatment of acute/chronic pain. To present an update on the existing evidence base for research and clinical practice supporting acupuncture analgesia. This Clinical Update elaborates on the 2023 International Association for the Study of Pain Global Year for Integrative Pain Care "Factsheet Acupuncture for Pain Relief" and reviews best evidence and practice. Acupuncture is supported by a large research evidence base and growing utilization. Mechanisms of acupuncture analgesia include local physiological response at the needling site, suppression of nociceptive signaling at spinal and supraspinal levels, and peripheral/central release of endogenous opioids and other biochemical mediators. Acupuncture also produces pain relief by modulating specific brain networks, integral for sensory, affective, and cognitive processing, as demonstrated by neuroimaging research. Importantly, acupuncture does not just manage pain symptoms but may target the sources that drive pain, such as inflammation, partially by modulating autonomic pathways. Contextual factors are important for acupuncture analgesia, which is a complex multifaceted intervention. In clinical practice, historical records and many providers believe that acupuncture efficacy depends on specific acupoints used, the technique of needle placement and stimulation, and the person who delivers the procedure. Clinical research has supported the safety and effectiveness of acupuncture for various pain disorders, including acupuncture as a complementary/integrative therapy with other pain interventions. Although the quality of supportive evidence is heterogeneous, acupuncture's potential cost-effectiveness and low risk profile under standardized techniques suggest consideration as a neuromodulatory and practical nonpharmacological pain therapy.

Optimal blood pressure control with fewer antihypertensive medications: Achieved mostly in low-risk hypertensive patients.

Recent studies indicate that intensive blood pressure (BP) targets can be reached with less than two medications. This cross-sectional study, involving 4991 individuals from the Majiapu community, assessed the correlation between BP control and the burden of antihypertensive drugs. Participants on medication were categorized into controlled (BP<140/90mm Hg) and uncontrolled (BP≥140/90mm Hg) groups, with the former further divided into optimal (BP<130/80mm Hg) and good control (BP<140/90 but >130/80mm Hg) subgroups. Multivariate logistic regression analyzed factors affecting hypertension control across these BP categories. The study found that, 54% of participants had hypertension. Of those treated (62.5%), 55.7% achieved BP control, including 23.15% maintaining BP below 130/80mm Hg. The average number of antihypertensive medications was 1.61 for the controlled group (with an average BP of 126.6/76mm Hg) and 1.75 for the uncontrolled group (with an average BP of 150.6/84.0mm Hg). Additionally, the average number of antihypertensive medications was 1.66 in the good control group and 1.55 in the optimal control group. The uncontrolled group had a higher mean systematic coronary risk estimation (SCORE) of 5.59, against 3.97 and 2.5 in the good and optimal control groups, respectively. Key factors linked to poor BP control included age over 65, male sex, obesity, and former smoking, whereas lipid-lowering medication use was associated with better control. In conclusions, patients needing fewer antihypertensive drugs to achieve stricter targets may have a lower risk profile. Notably, only a small proportion of treated patients are low-risk individuals who can easily achieve BP levels below 130/80mm Hg.

Heterogeneous Treatment Effects in the Incredible Years Teacher Classroom Management Programme - A Latent Profile Approach

Heterogeneous effects from interventions often remain hidden in between-group analyses, risking overgeneralized conclusions of treatment effects. In this exploratory study, we performed latent profile analysis to unveil differential treatment effects among children in The Incredible Years Teacher Classroom Management Programme (IY TCMP). This program has previously been shown to reduce behavioral problems in preschools and schools in total samples and subgroups. A total of 726 children (48.7% girls; Mage = 4.21 years; SDage = 0.86) from 92 childcare centers in Norway participated in either the intervention (n = 338) or the matched control condition (n = 388). First, by conducting latent profile analysis on baseline levels of child-teacher relationship (closeness, conflict), behavioral problems, and social competence, three distinct profiles were identified: High Risk (26.4%), Moderate Risk (42.8%), and Low Risk (30.7%) – each profile with unique characteristics. Second, we tested for within-profile, condition-by-time interactions following the intervention, showing distinct treatment responses for each profile. High-risk profiles profited most from the IY TCMP, with a substantial decrease in externalizing problems, more teacher closeness, and less teacher conflict. Moderate-risk profiles also gained better teacher-child relationships and improved social competence. The Low-Risk profiles showed no effects from the intervention. It is argued that latent profile analysis presents a feasible approach for examining within-sample heterogeneity in intervention research. It also reveals crucial information on treatment variability, as demonstrated in the Incredible Years Programme.

The Impact of Policy Quality and Political Stability on Foreign Direct Investment in ASEAN Countries: An Institutional Economics Analysis

This investigation pivots on the impact of policy quality and political stability on foreign direct investment within ASEAN countries. Both facets form essential components of a country's political risk profile; a lower risk profile, characterized by sturdy policy quality and political stability, tempts investors to channel their capital into preferred investment destinations. Our research employs a panel data regression analysis across seven ASEAN nations; Indonesia, Malaysia, Singapore, Thailand, Vietnam, the Philippines, and Brunei Darussalam, from 2012 to 2022. The Common Effects Model emerged as the optimal panel model during our study. We found that policy quality negatively impacts foreign direct investment, signifying that investments are perceived unprofitable due to the policy quality in the ASEAN region. In counterpoint, political stability has a positive effect, confirming that stable political circumstances in the ASEAN region draw investor interest. These significant findings validate that policy quality and political stability significantly sway foreign direct investment within ASEAN countries, making them crucial considerations for prospective investors.