Benefits Of Treatment Research Articles

Icosapent ethyl by baseline small dense low-density lipoprotein cholesterol: an analysis of REDUCE-IT

Abstract Background Small dense low-density lipoprotein cholesterol (sdLDL-C) is associated with cardiovascular (CV) risk. Purpose We assessed if baseline sdLDL-C modified the effect of icosapent ethyl among patients in REDUCE-IT. Methods REDUCE-IT randomized patients to icosapent ethyl vs placebo. In this post hoc analysis, patients ≥45 years with CV disease or ≥50 years with diabetes and CV risk factors were included. Patients were required to have triglycerides of 135-499 mg/dL and low-density lipoprotein cholesterol (LDL-C) of 41-100 mg/dL. Exclusion criteria included severe heart failure, acute severe liver disease, or hemoglobin A1c >10%. Patients were stratified by baseline calculated sdLDL-C. A threshold of 46 mg/dL was chosen because sdLDL-C greater than this cutoff has predicted CV risk despite well-controlled LDL-C. The primary outcome included a composite of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina. The key secondary composite outcome included CV death, nonfatal MI, or nonfatal stroke. Outcomes were assessed with Cox proportional hazard models and interaction analyses were conducted to assess heterogeneity in treatment effect by baseline sdLDL-C. Results REDUCE-IT included 8179 patients, with 8157 (99.7%) patients having sdLDL-C data. Among these patients, 7698 (94.4%) had sdLDL-C <46 mg/dL and 459 (5.6%) had sdLDL-C ≥46 mg/dL. Median sdLDL-C was 34.2 mg/dL (interquartile range [IQR]: 30.3, 38.4 mg/dL) in the lower sdLDL-C group and 48.4 mg/dL (IQR: 47.1, 50.6 mg/dL) in the higher sdLDL-C group (Table). The placebo group had a greater event rate in the higher sdLDL-C group compared to the lower sdLDL-C group (72.0 vs 56.4 events per 1000 p-y), though event rates in the icosapent ethyl group were similar by sdLDL-C group (44.1 vs 43.3 events per 1000 p-y, respectively). Icosapent ethyl reduced the rate of the primary outcome compared with placebo (17.2% vs 22.0%; hazard ratio [HR]: 0.75 [95% CI: 0.68, 0.83]; P<0.0001). The number needed to treat [NNT] to avoid one primary endpoint event was 21. In the lower sdLDL-C group, icosapent ethyl decreased rates of the primary outcome (43.3 events per 1000 patient-years [p-y]) compared with the placebo group (56.4 events per 1000 p-y) (17.3% vs 21.7%; HR: 0.77 [95% CI: 0.69, 0.85]; NNT: 22). Similarly, in the higher sdLDL-C group, icosapent ethyl decreased the rate of the primary outcome (44.1 events per 1000 p-y) compared with the placebo group (72.0 events per 1000 p-y) (16.6% vs 26.4%; HR: 0.58 [95% CI: 0.38, 0.88]; NNT: 10). There was no significant interaction between treatment benefit and baseline sdLDL-C for the primary (Pinteraction = 0.22) and key secondary outcome (Pinteraction = 0.82). Findings were overall similar for the other secondary outcomes (Figure). Conclusion Icosapent ethyl reduced CV outcomes in patients with high CV risk and elevated triglycerides irrespective of low or high sdLDL-C.

Identifying clinical phenotype clusters for coronary artery disease: a novel approach using clustering by unsupervised machine learning

Abstract Background Guideline recommendations for the prevention of cardiovascular (CV) events in patients with coronary artery disease (CAD) are one-size-fits-all. Clinically identifiable phenotypes needing specific considerations might exist. Purpose To identify phenotypes in patients with CAD based on clinical characteristics and their relationship with the risk of new CV events and treatment benefits. Methods Unsupervised machine learning through latent class analysis (LCA) was performed on patients with CAD included in the UCC-SMART cohort (n = 5,888) and SWEDEHEART registry (n = 67,428), to identify patient clusters (i.e., phenotypes) based on clinical characteristics: age, sex, body-mass-index, diastolic blood pressure, history of diabetes, myocardial infarction, atrial fibrillation, polyvascular disease, current smoking, non-high density lipoprotein cholesterol, estimated glomerular filtration rate, and C-reactive protein. Number of clusters was determined using the Bayesian information criterion. Event free survival and hazard ratios (HR) for major adverse cardiovascular events (MACE) as primary endpoint, including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, were estimated per cluster. The LCA were performed in each respective cohort and cross-validated in the other cohort to assess impact of variations in clustering variables on cluster reproducibility. In UCC-SMART, bootstrapping was performed the assess stability of the LCA model and impact on cluster assignment. Results In UCC-SMART four distinct phenotypes within the CAD population could be distinguished: Phenotype A (16%) of mostly males with isolated CAD, phenotype B (30%) of older patients with polyvascular disease, Phenotype C (28%) of only women with limited traditional risk factors and Phenotype D (27%) young, current smokers with a premature event (Figure 1). Cross-validation in SWEDEHEART identified roughly the same four phenotypes, i.e., phenotype A (39%) with 100% males and 3.8% polyvascular disease, phenotype B (8%) with average age of 71 years and 30% polyvascular disease, phenotype C (19%) with 100% women, and phenotype D (34%) 54 years and 25% current smokers. Notably, although age was comparable between phenotype A and C, MACE-free survival was worse for the female-only cluster. Similarly, although patients where on average 9 years younger in phenotype D when compared to phenotype A, MACE-free survival was worse (Figure 2). No significant changes in clustering models were observed in the bootstrap samples. Conclusion Phenotypes can be distinguished within patients with CAD. These phenotypes are related to differences in the risk of recurrent events. These findings suggest that specific guideline recommendations for these groups could be considered.Cluster interpretation in SMARTSurvival along cluster lines

Benefits of Rhythmic Auditory Stimulation and Lee Silverman Voice Treatment in a Parkinson’s Disease Patient With Meningoencephalitis: A Case Report

Benefits of Rhythmic Auditory Stimulation and Lee Silverman Voice Treatment in a Parkinson’s Disease Patient With Meningoencephalitis: A Case Report

Characterization of Sulfur Oxidizing Bacteria and Their Effect on Growth Promotion of Brassica napus L.

Oil seeds sector is one of the major dynamic components of the agriculture world. Oil seeds such as canola (Brassica napus) require a higher quantity of sulfur (S), which is supplied through inorganic fertilizers. However, the overapplication of agro-chemicals to get higher yields of crops is harming the soil health. Therefore, the application of bacterial cultures with plant growth-promoting activity as biofertilizers ensures soil health maintenance and enhances crop productivity. To achieve this aim, the present research was initiated by procuring three sulfur-oxidizing bacteria (SOBs), namely, SOB 5, SOB 10, and SOB 38, from the Microbiology Department, PAU. In the initial assessment, all three SOB cultures showed resilience to pesticide toxicity at the recommended dosage, with the exception of ridomil. These cultures were later characterized morphologically, biochemically, and at the molecular level using 16s rRNA resulting in their identification as Enterobacter ludwigii strain Remi_9 (SOB 5), Enterobacter hormaechei strain AUH-ENM30 (SOB 10), and Bacillus sp. 5BM21Y12 (SOB 38). Functional characterization of these SOB cultures revealed their ability to exhibit multifarious plant growth-promoting traits. Bacillus sp. 5BM21Y12 showed greater functional activity, including high P solubilization (14.903 µg/mL), IAA production (44.28 µg/mL), siderophore production (13.89 µg/mL), sulfate ion production (0.127 mM), ammonia excretion (2.369 µg/mL), and Zn solubilization (22.62 mm). Based on the results of functional and molecular characterization, Bacillus sp. 5BM21Y12 was selected for field trials by formulating different treatments. Composite treatment, T8 (100% S + Bacillus sp. + pesticides) significantly enhanced growth parameters (plant height, root, and shoot biomass), yield attributes (siliqua length, test weight, number of siliqua/plant), yield parameter (total biomass and seed yield), quality parameter (crude protein and oil) as compared to all other sole treatments employed in the field. A combined application of non-pathogenic Bacillus sp. 5BM21Y12, with good functional activity enhanced yield of crop due to synergistic and additive interaction with fertilizer/pesticides. As biofertilizer application reduces the input of pesticides/fertilizers new inoculant formulations with cell protectors and the development of compatible pesticides should be searched to assure the benefits of integrated treatment.

Unraveling immune checkpoint inhibitors effects on atherosclerosis: mechanisms and preventive approaches

Abstract Background Immune checkpoint inhibitors (ICIs) represent a novel and rapidly evolving field in cancer treatment. Despite increasing reports of accelerated atherosclerosis and ICI-related atherosclerotic cardiovascular (CV) events in clinical studies and case reports, there is a notable lack of data concerning the underlying mechanisms, appropriate monitoring, and potential interventions. Objectives To explore the role of ICIs in triggering and/or accelerating the atherosclerotic process, with a specific focus on the involvement of CD8+ T-cells. Additionally, we aimed to evaluate and compare the potential beneficial effects of statins and Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors on atherosclerosis under ICIs treatment. Methods Thirty 8-week-old C57BL mice were divided into six groups as follows: (1) Control, normal diet; (2) Control, atherogenic diet; (3) Atherogenic diet + anti PD-1; (4) Atherogenic diet + statins + anti-PD1; (5) Atherogenic diet + PCSK9-i + anti PD-1; (6) Atherogenic diet + PCSK9 inhibitors. At 16 weeks, the carotid arteries and heart were removed for histological examination, and serum was withdrawn for blood work and further analysis. Results Anti-PD1 treatment resulted in extensive lymphocytic infiltration of the carotid intima, primarily constituted of CD8+ T cells. This infiltration was significantly attenuated when statins or PCSK-9 inhibitors were used in conjunction with anti-PD1 treatment. Serum analysis for CD4+ and CD8+ T cells by ELISA revealed no difference in CD4+ abundance between the groups. However, plasma CD8+ T cells were significantly increased with anti-PD1 treatment, and furthermore, when PCSK9 inhibitors were used in combination; but not when statins were used. Conclusion The induction of CD8+ T cell infiltration in the arterial carotid walls by anti-PD-1 was prevented with the use of either statins or PCSK9 inhibitors. In the plasma, while statins reduced the hyper-expression of CD8+ T cells observed under PD-1 treatment, PCSK9 inhibitors enhanced this expression. This may provide a first indication of the potential benefit of PCSK9 inhibitor treatment for both preventing arterial inflammation and enhancing the desired anti-tumor immune response under ICIs treatment. Figure legend: 1A. A cross-section of the carotid artery after 16 weeks of treatment, stained with H&E. Magnification is X100. 1B. A cross-section of the carotid artery after 16 weeks of treatment, stained with anti-CD8 Ab. Magnification is X100. 1C. quantitative CD8+ T cells staining in the carotid arteries. 1D. quantitative results of ELISA for plasma CD8+ T cells.

Home blood pressure control and prescribing patterns of anti-hypertensive medications in a home blood pressure-based hypertension-specialized clinic in Japan: a sub-analysis of the Ohasama study.

Although the benefits of anti-hypertensive treatment are well known, the proportion of hypertensive patients with controlled blood pressure (BP) remains suboptimal. The present study aimed to compare BP control conditions in a hypertension-specialized clinic and non-hypertension-specialized clinics. This cross-sectional study used data from 379 treated patients who measured home BP in the Ohasama study between 2016 and 2019 (men: 43.0%, age: 71.6 years). Of those, 172 patients were managed at the hypertension-specialized clinic where physicians distributed home BP devices to each patient, evaluated the home BP data, and adjusted medications to maintain home BP values according to the recent Japanese guidelines. When we set morning home systolic/diastolic BP of <135/ < 85 mmHg as controlled BP, 93.6% of patients fulfilled the controlled home BP range, compared to 43.0% in non-specialized clinics (n = 207). The proportion of the patients with home morning BP < 125/ < 75 mmHg was 73.3% in the hypertension-specialized clinic and 20.8% in the non-hypertension-specialized clinics. Hypertension-specialized clinics prescribed three or more anti-hypertensive drug classes to 41.9% of patients, compared to 15.2% in non-specialized clinics. In the hypertension-specialized clinic, angiotensin II receptor blockers were most commonly prescribed (86.6%), followed by dihydropyridine calcium channel blockers (77.9%), thiazide (including thiazide-like) diuretics (30.2%), mineralocorticoid receptor blockers (23.8%), and beta- and alpha-beta blockers (10.5%). In conclusion, the proportion of patients with controlled home BP was excellent in the hypertension-specialized clinic. Home BP-based hypertension practices, as recommended in the current Japanese guidelines, may be the key to achieving sufficient BP control.

Diastolic dysfunction and survival in patients with preserved or mildly reduced left ventricular ejection fraction

Abstract Background Left ventricular ejection fraction (LVEF) is relatively indiscriminate for prognosis in patients with preserved or mildly reduced LVEF (&amp;gt;40%) following myocardial infarction (MI). Aims This study sought to determine the value of guideline-based assessment of diastolic dysfunction (DD) in predicting all-cause and cardiac mortality in patients with a first-ever MI and LVEF&amp;gt;40%. Methods A retrospective single centre study involving 2234 patients with a first-ever MI (STEMI or NSTEMI) with LVEF&amp;gt;40% was performed. Clinical, angiographic, and echocardiographic data were obtained from prospectively maintained institutional databases. Outcomes data were obtained from the state-wide registry. Echocardiography was performed early post-admission for all patients. Significant diastolic dysfunction (DD) was defined as grade 2+3 diastolic dysfunction according to current American Society of Echocardiography/ European Association of Cardiovascular Imaging guidelines. Results The mean age of patients was 61.4±12.3 years, 70.7% were males, and 12.1% had 3-vessel disease. The mean LVEF was 55.8±7.2% and 9.1% had significant DD. At a median follow up of 4.5 years, there were 219 deaths (46 cardiac deaths). On Cox proportional hazards multivariable analyses incorporating significant clinical, angiographic, and echocardiographic variables, significant DD was an independent predictor of both all-cause (HR 2.01,95%CI 1.37-2.94, p&amp;lt;0.001) and cardiac (HR 3.97,95%CI 1.98-7.99, p&amp;lt;0.001) mortality. Conclusions Significant DD is an independent predictor of all-cause and cardiac mortality following MI in patients with preserved or mildly reduced LVEF and thus effectively re-stratifies prognosis in a subgroup where the LVEF is relatively indiscriminate for survival. The benefit of further investigation and/or treatment in this subgroup needs further study.

Impact of appendicular skeletal muscle mass on effect of intensive blood pressure control

Abstract Background Appendicular skeletal muscle mass (ASM) is associated with cardiovascular diseases (CVDs) and chronic kidney diseases (CKDs). However, whether low ASM affects the efficacy of intensive systolic blood pressure control is currently uncertain. Purpose To examine the impact of low ASM on the effects of intensive SBP control on cardiovascular and kidney outcomes. Methods Data from the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trials was used. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. The prespecified incident CKD was defined as a &amp;gt;30% decrease in estimated glomerular filtration rate to a value &amp;lt;60 mL/min/1.73 m2. Results A total of 14,017 patients were included in this study, 2203 (15.7%) of whom had low ASM. Over a median follow-up of 3.26 years, 1,032 primary outcomes and 460 incident CKD were observed. Patients with low ASM had a significantly higher risk of primary outcome and CKD. Intensive SBP control effects on cardiovascular outcomes were not significantly different on a relative scale or absolute scale. But low ASM significantly amplified the increased risk of CKD associated with intensive SBP control, on an absolute scale (P for interaction = 0.04). Conclusions Low ASM is one of the markers of increased risk of CVD and CKD, and it did not affect the cardiovascular benefits of intensive treatment, but significantly amplified the increased risk of CKD associated with intensive SBP control.

Cardiac damage predicts the outcome of calcific aortic valve disease regardless of the severity of aortic stenosis

Abstract Title: Cardiac damage predicts the outcome of patients with calcific aortic valve disease in both mild and moderate aortic stenosis Background Although the burden of calcific aortic valve disease (CAVD) is increasing, there is no current universal consensus for prognostic prediction. A staging system based on cardiac damage has been proposed to better stratify risk and evaluate the benefit of aortic valve intervention (AVI). Purpose We sought to evaluate this staging system’s prognostic value in mild and moderate aortic stenosis (AS). Methods Data from clinically indicated echocardiograms performed between 2010 and 2018 in patients aged over 18 years were extracted and linked to national outcome data. A time to first event analysis was performed with a primary outcome of mortality or heart failure hospitalization. Stages were categorized as described in previous literature: no extravalvular damage (stage 0); left ventricular damage (stage 1); left atrial damage (stage 2); elevated right ventricular pressures (stage 3); or right ventricular damage (stage 4). Results Amongst 24,699 patients in the study cohort, 513 had moderate AS and 920 had mild AS. Associated cardiac damage in those with moderate AS was graded as follows: Stage 0 - 9.4%; Stage 1 - 53.7%; Stage 2 - 31.1%; Stage 3 - 3.2%; Stage 4 - 2.6%. Increasing severity of CAVD correlated closely with increased risk of the primary outcome in both moderate (HR 1.62 per stage; 95% CI 1.36 – 1.92) and mild AS (HR 1.93 per stage; 95% CI 1.69 – 2.21), whilst increasing stage of cardiac damage was associated with mortality when censoring at the time of AVI in both moderate (HR 1.97 per stage; 95% CI 1.66 – 2.34) and mild AS (HR 2.06 per stage; 95% CI 1.81 – 2.35). Conclusion Cardiac dysfunction predicts prognosis to a similar extent in both mild and moderate AS. These data suggest that adverse outcomes may not be fully attributable to the haemodynamic consequences of valve disease, and therefore may not be reversed by valve intervention. Strategies to treat cardiac dysfunction in parallel with management of the anatomical valve pathology may be required.Mortality in mild AS by CAVD stageMortality in moderate AS by CAVD stage

Design considerations for future affective automotive interfaces: a review of self-regulation strategies to manage affect behind the wheel

Like inattention, dysregulated emotions can seriously distract motorists and disrupt their driving performance. The current review examined the literature on emotion regulation to find relevant strategies for managing intense emotions while driving a motor vehicle. Next, we considered whether those relevant strategies could be used to design future affective automotive interfaces. Results suggested that problem-solving, task-focused coping, mindfulness, and relaxation effectively regulate emotions while driving. These findings highlight that some strategies may be effective but costly to implement while driving (cognitive reappraisal and distraction), which need to be better understood before implementing them into automotive interfaces. Together, these findings suggest the potential benefits of embedding self-regulatory interventions in future automotive interfaces that can help maintain an optimal affective state to reduce distraction and improve safe driving.

Social Inequalities in mental health service use and perceived helpfulness: A global analysis across 111 countries

Abstract Social inequalities in mental health are evident in the prevalence of mental health problems, but also the utilisation and patents’ perceived benefits of treatment. However, the extent of these disparities on a global scale and whether there are country-level differences in the predictors of mental health service use remain unknown. This study uses data from the Wellcome Global Monitor 2020, a nationally representative survey encompassing 111 countries and 117,088 individuals. We examine the association of socio-economic factors (such as household income and education), psycho-social factors (including stigma perception and trust in health professionals), and country-level variables (such as GDP, Gini coefficient, and health expenditure) with mental health service use and perceived effectiveness of treatment. Multi-level logistic regression models were employed for analysis. The utilisation of mental health professions of people with depression or anxiety symptomology is higher in HICs (predicted probability of 62% CI[0.60 - 0.65]) compared to LIMCs (predicted probability of 33% CI[0.31 - 0.34]). Higher country GDP (OR = 1.26 CI[1.08-1.47]) and health expenditure (OR = 1.11 CI[1.04-1.19] per percentage of health expenditure) are associated with higher treatment utilisation. On the individual level, those in the wealthiest quintile are more likely to engage with mental health professionals (OR = 1.25[1.14-1.36]) and perceive this treatment as highly beneficial (OR = 1.23[1.07-1.40]). Trust in healthcare practitioners and perceived stigma are also associated with mental healthcare use. This analysis shows strong patterns of mental healthcare use and perceived benefits depending on the wealth of the country, health expenditure and individual socio-economic status. Moreover, disparities in treatment utilization and effectiveness are also influenced by trust in healthcare professionals and perceived mental health stigma.

A method for interactive collaboration between different actors: theory of change workshops

Abstract It is well recognised that the involvement of different actors in health research is crucial to the success of projects and interventions, as it increases the likelihood that they will be relevant, impactful and applicable in practice. However, researchers and policy makers often lack tools for the participatory involvement of actors. One way of actively involving actors is the Theory of Change (ToC) method. A ToC is a model of a change process that describes how and why an intervention leads to the intended change or outcome in a given context. It describes the path along which change is expected to occur and provides a framework for investigating whether and how change takes place. It is a systematic methodology that can be used both prospectively and retrospectively for the planning, implementation and evaluation of interventions. The approach recognises that changes in socio-ecological systems are complex and challenging and that the causal processes are often non-linear and intertwined. A ToC workshop begins with the formulation of a clear vision for the desired change and the long-term goal of the intervention. Starting from the long-term goal, the necessary medium-term and short-term goals are then defined in a backward mapping process. Next, indicators, activities and assumptions are defined for each intermediate goal. The results of a ToC workshop can be visualised in a ToC map, which shows the causal pathways, relationships, and connections between the different components of the ToC. This visual representation helps the actors to understand the logic, connections, and assumptions underlying the ToC. This in turn facilitates a shared understanding, collaboration, and ownership among all actors involved. Overall, successful involvement of actors using the ToC method can not only enrich the research process, but ultimately also increase the health benefits of interventions and health policies.

Gender identity differences in age of first mental health diagnosis: A population-based study of childhood and adolescence

Abstract Introduction Gender minority (GM; i.e., trans, non-binary, and other gender diverse) individuals have an increased risk of mental health disorders, but few studies have explored disparities using population-based samples or the age of onset of this risk. Objectives The aim of the current study was to identify the age at which the gender identity disparity in physician-assessed psychiatric diagnosis and treatment for common mental health disorders can be first identified in a population-based sample linked to national health care registries. Methods All individuals aged 16 to 25 (n = 18,793) participating in the nationwide probability-based Swedish National Public Health Survey in 2018, 2020, or 2021 were included in the analyses. This sample could be linked to mental health care treatment history data in nationally comprehensive health care registries starting at age 8 years old. Results Individuals reporting a GM identity in adulthood were seven times more likely to having been diagnosed with depression and/or anxiety and about five times more likely to having been diagnosed with a neurodevelopmental disorder during childhood or adolescence compared to individuals with a cisgender identity. GM individuals’ increased likelihood of being diagnosed with depression and/or anxiety was significantly elevated from age 13, while their neurodevelopmental disorder diagnosis risk was significantly elevated from age 10, compared to cisgender individuals. Conclusions The results from this study are the first population-based evidence to show that GM individuals are more likely to be diagnosed and treated for mental health disorders early during childhood and adolescence compared to cisgender individuals. The early emergence of this increased risk requires further inquiry into causes of these early disparities. It also suggests a potential benefit of interventions that facilitate social belonging and inclusion and reduce stressors related to societal expectations of gender.

Race in heart failure: a pooled participant-level analysis of the global PARADIGM-HF and PARAGON-HF trials

Abstract Background Mechanisms of disease pathobiology, prognosis, and potentially treatment responses might vary by race in patients with heart failure (HF). Early experiences with neprilysin inhibition suggested possible increased risks of angioedema, especially among Black individuals. We aimed to examine the safety and efficacy profile of sacubitril/valsartan in a pooled participant-level dataset of 2 large cohorts of patients with HF by self-reported race. Methods PARADIGM-HF and PARAGON-HF were multicenter, randomized clinical trials testing sacubitril/valsartan against a renin-angiotensin system inhibitor (RASi, enalapril or valsartan, respectively) in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF). We included all patients with available data on self-reported race and categorized patients as White, Asian, or Black. We assessed adjudicated outcomes including the composite of first HF hospitalization (HFH) or cardiovascular (CV) death, its components, and angioedema by racial group. Results Among 12,097 included participants, 9,451 (78.1%) were White, 2,116 (17.5%) were Asian, and 530 (4.4%) were Black. Asian participants were from 19 countries, with highest enrollment from India, China, and the Philippines. Black participants were from 18 countries, with highest enrollment from the US, South Africa, and Brazil. Black patients had the worst baseline health status (adjusted KCCQ-OSS mean 70.3), while White (71.4) and Asian patients (76.4) had better health status; P&amp;lt;0.001. Over 2.4-years of median follow-up, Black (adjusted HR 1.67; 95% CI 1.37-1.89; P&amp;lt;0.001) and Asian patients (adjusted HR 1.32; 95% CI 1.16-1.50; P&amp;lt;0.001) experienced higher risks of the primary outcome compared with White patients (Figure 1). The treatment effects of sacubitril/valsartan vs. RASi on the primary endpoint were consistent among White (HR 0.84; 95% CI: 0.77-0.91), Asian (HR 0.92; 95% CI: 0.78-1.10), and Black patients (HR 0.79; 95% CI: 0.58-1.07; Pinteraction = 0.39). In light of higher baseline risks, Black patients accrued the greatest absolute risk reduction with sacubitril/valsartan (Figure 2). Consistent treatment benefits by race were also observed for the individual components (CV death alone and first HFH alone). Rates of any adjudicated angioedema were numerically higher with sacubitril/valsartan vs. RASi across race groups (White 0.4% vs. 0.2%; Asian 0.6% vs. 0.2%; Black 2.3% vs. 0.8%), however no patient in either trial experienced airway compromise or required mechanical airway protection. Conclusions In a pooled experience of over 12,000 participants enrolled in 2 trials conducted across 56 countries, Black and Asian patients exhibited a higher risk of CV events than White patients. Rates of non-serious angioedema were numerically higher with sacubitril/valsartan across race groups. The relative CV benefits of sacubitril/valsartan were consistent across races, with greatest absolute benefits observed in Black patients.

Peer support interventions improve disease self-management after coronary heart disease diagnosis: a systematic review and meta-analysis

Abstract Background Patients with coronary heart disease (CHD) diagnoses often experience impacts on patient-reported outcomes (quality of life, depression, disease self-management and self-efficacy) at a time when secondary prevention is required. Peer support has proven benefits for these issues in many chronic conditions but synthesis of the evidence in CHD populations has not been undertaken. Purpose In this systematic review and meta-analysis, we aimed to explore the impact of peer support interventions on health-related quality of life, depression, anxiety, self-management and self-efficacy in CHD. Methods Electronic databases were searched from inception to November 2023 (MEDLINE, Embase, PsycINFO, CINAHL, Scopus, PubMed [non-MEDLINE], Web of Science, and the Cochrane Central Register of Controlled Trials). Randomised controlled trials (RCTs) evaluating peer support interventions (that enable experience sharing and/or support by others with the same condition) in populations with diagnosed CHD were eligible for inclusion. Risk of bias was assessed using the Cochrane risk of bias tool. Meta-analyses were undertaken in RevMan Version: 7.4.0 using the inverse variance method and a random effects model. Results In total, 16 papers reporting 14 unique RCTs were included. The total sample (n=1793) was 65% male with a mean age of 54.5±13.0 years. The diagnosis of the samples varied between studies, including coronary artery bypass graft(s), first time or newly diagnosed myocardial infarction and percutaneous coronary intervention. By 6-months follow-up, peer support interventions demonstrated no statistically significant improvements in health-related quality of life (SMD -0.38, 95% CI -1.84, 1.08), depression (SMD -0.09, 95% CI -0.26, 0.08) and anxiety (SMD -0.85, 95% CI -1.83, 0.14). Whereas, improvements occurred in disease self-management (SMD 1.49, 95% CI 0.66, 2.32) and self-efficacy in both short term (by 6-months, SMD 0.57, 95% CI 0.37, 0.77) and longer term (6-12 months, SMD 0.67, 95% CI 0.29, 1.05). Peer support interventions varied widely in format and several studies were of poor quality. Conclusion Peer support interventions benefit patient-reported outcomes of disease self-management and self-efficacy up to 6 and 12 months, but not for other patient reported outcomes after CHD diagnosis. More exploration is needed of content, delivery and focus of peer support interventions to maximise effectiveness for CHD secondary prevention.

NIR-Guided Coating Optimization of Omega-3 Fatty Acid Mini Soft Capsules with Pitavastatin and Ezetimibe

Background: This study aimed to optimize the coating process of Omega-3 fatty acid (OM3-FA) mini soft capsules containing the active pharmaceutical ingredients (APIs) pitavastatin and ezetimibe using near-infrared (NIR) spectroscopy for in-process monitoring. Cardiovascular disease treatments benefit from combining OM3-FA with lipid-lowering agents, but formulating such combinations in mini soft capsules presents challenges in maintaining stability and mechanical integrity. Methods: The coating process was developed using a pan coater and real-time NIR monitoring to ensure uniformity and quality. NIR spectroscopy enabled precise control of coating thickness, ensuring consistent drug distribution across the capsule surface. Results: The optimized process minimized OM3-FA oxidation and preserved the mechanical integrity of the capsules, as confirmed by texture analysis and in-vitro dissolution testing. This integration of NIR spectroscopy as a process analytical technology (PAT) significantly improved coating quality control, resulting in a stable and effective combination therapy for pitavastatin and ezetimibe in a mini soft capsule form. Conclusion: This approach offers an efficient solution for enhancing patient adherence in cardiovascular disease management. The application of NIR spectroscopy for real-time monitoring highlights its broader significance in pharmaceutical manufacturing, where it can serve as a versatile tool for ensuring product quality and optimizing production efficiency in diverse formulation processes. By incorporating NIR-based PAT, manufacturers can not only achieve product-specific improvements but also establish a foundation for continuous manufacturing and automated quality assurance systems, ultimately contributing to a more streamlined and robust production environment.

Effect of the glucagon-like peptide-1 receptor agonists on diabetic peripheral neuropathy: A meta-analysis.

Previous researches found that glucagon-like peptide 1 receptor agonists (GLP-1RA) offer benefits beyond their anti-diabetic properties, including weight loss and cardiovascular disease prevention. However, the effects of GLP-1RA on diabetic peripheral neuropathy (DPN) remain unclear. This meta-analysis aims to assess the potential benefits of GLP-1RA treatment in DPN patients by evaluating peripheral neural function. Following the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a meta-analysis of the clinical trials investigating the impact of GLP-1RA treatment on peripheral neural function in patients with DPN. Outcomes were measured using electrophysiological tests, including nerve conduction velocity (NCV) and action potential amplitude. Our meta-analysis included six studies with 271 participants. Following GLP-1RA treatment, NCV significantly improved compared to the control group (MD 1.74; 95% CI 1.16 to 2.33; p < 0.001) and before treatment (MD 2.16; 95% CI 1.04 to 3.27; p < 0.001). Despite the improvement in NCV, blood glucose levels did not change significantly (MD -0.20 95% CI -0.87 to 0.46, p = 0.55) indicating that GLP-1RA enhances NCV through mechanisms other than glucose lowering. Nonetheless, as a result of the limited population studied, further research is needed to strengthen the reliability of these findings.

Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152. Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases. Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3. Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns. ClinicalTrials.gov: NCT03518086; NCT03524092; NCT03519945.

Effects of Traditional Chinese Martial Arts and Stretching Exercises on Symptoms of Fibromyalgia: A Systematic Review and Meta-Analysis.

Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread musculoskeletal pain and various associated symptoms. Non-pharmacological interventions have gained attention for managing FMS and improving patient outcomes. We reviewed past research to investigate the effects of traditional Chinese martial arts (TCMA) and stretching training (ST) on symptoms of patients with FMS. We searched Web of Science, Medline via PubMed, the Cochrane Library, and EMBASE from their inceptions to June 1, 2023. Across selected studies, we evaluated TCMA and ST using Fibromyalgia Impact Questionnaire (FIQ) scores, pain symptoms, fatigue levels, and sleep quality as outcome measures. Compared with control groups, participants receiving TCMA and ST interventions showed significantly lower FIQ scores (Standard Mean Difference (SMD) = -3.01, 95% Confidence Interval (CI) [-4.83,-1.19]), improved pain symptoms (SMD = -0.77, 95% CI [-1.07,-0.47]), less fatigue (SMD = 1.31, 95% CI [0.50,2.11]), and enhanced sleep quality (SMD = -0.55, 95% CI [-0.97,-0.12]). Subgroup analyses revealed that, irrespective of intervention duration, both TCMA and ST interventions were effective in relieving pain symptoms in these patients. ST interventions showed significant improvement in fatigue symptoms, while TCMA interventions positively influenced sleep quality. These findings highlight potential non-pharmalogical benefits of TCMA and ST interventions in managing FMS. However, future research should explore the optimal duration, frequency, intensity, and types of interventions for TCMA and ST and design targeted exercise intervention programs to study the effects of these interventions on different characteristics of FMS patients. Attention should be given to the effects of short-term interventions on improving fatigue symptoms, sleep quality, and pain relief, to provide more personalized and effective FMS treatment plans.

Discovering what young adults want in electronic interventions aimed at reducing alcohol-related consequences.

Despite intervention efforts, negative alcohol-related consequences continue to impact young adults. Most alcohol interventions focus on reducing alcohol consumption; however, previous research indicates that focusing solely on alcohol use may not decrease consequences. Additionally, many alcohol interventions have diminishing engagement, and few are designed with young adults involved in the development process. Drawing on user-centered design, this study sought to understand young adult perceptions, preferences, and needs for electronic interventions specifically aimed at reducing alcohol consequences. Using semi-structured qualitative interviews, 21 young adult drinkers (ages 18-24; 57.1% female) shared their opinions regarding the need for electronic interventions (i.e., mobile or web-delivered) to reduce alcohol consequences as well as their preferences for content, features, and ways to increase engagement. Interviews were coded and analyzed using a multi-step thematic analysis approach. As part of our discovery phase of intervention development, content coding revealed four main themes. Participants perceived several benefits of interventions focused on alcohol consequences, such as promoting mindful alcohol use and reducing alcohol-related harms. Participants also discussed perceived limitations of such programs, including believing consequences from drinking are unavoidable, necessary for learning, and associated with peer pressure. Preferences for features included real-time tracking, personalized feedback, and psychoeducation along with preferences for design including non-judgmental framing, interactive content, and a user-friendly platform. Engaging end users early in the development process is a valuable approach to increase intervention relevancy with the target population. This can also inform intervention content and design to maximize engagement and satisfaction (e.g., framing, features, and interactivity) while also reducing barriers identified early on (e.g., peer pressure).