Background: Bridge symptoms connect different symptom clusters in a network and may serve as precise intervention targets. This study aimed to explore the bridge symptoms between somatic symptoms and anxiety and depressive symptoms among patients recovering from stroke using network analysis. Methods: A cross-sectional survey was conducted among 691 patients recovering from stroke who were recruited by convenience sampling from two tertiary hospitals. Symptom networks were estimated using the extended Bayesian information criterion (EBIC) graphical least absolute shrinkage and selection operator (GLASSO) method in R (qgraph package). The expected influence of the bridge was calculated to identify bridge symptoms, and network stability was assessed by bootstrapping (correlation stability [CS] coefficient). Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). Results: The symptom network demonstrated satisfactory stability (CS coefficient = 0.361 for bridge expected influence). The strongest edge was observed between HADS-A3 and HADS-D3 ( r = 0.879). PH6 was negatively associated with HADS-A1 ( r = −0.222) and positively associated with HADS-A6 ( r = 0.058). The top two bridge symptoms ranked by expected influence were HADS-D6 and HADS-A6. Conclusion: Two bridge symptom pairs were identified in the stroke recovery network: HADS-A3/HADS-D3, bridging anxiety and depressive symptoms, and HADS-D6/HADS-A6, linking somatic symptoms with depressive and anxiety symptoms. These bridging nodes may serve as promising intervention targets to disrupt cross-cluster symptom propagation and reduce overall symptom burden.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, but in practice it rarely occurs alone. Psychiatric, neurological, and even physical comorbidities occur alongside it. These complications may influence the diagnosis of the disorder, the choice of appropriate treatment, and long-term health outcomes. In this study, we described the most common of these in people with ADHD: epilepsy, tics, cardiovascular disease, metabolic disorders, chronic kidney disease, respiratory problems, and musculoskeletal disabilities. We review both pharmacological and non-pharmacological treatments. Our main emphasis is on individualized approaches that both address ADHD symptoms and do not affect patient safety. Our goal in this review is to provide a comprehensive, evidence-based overview of these comorbidities and demonstrate that how much coordinated, multidisciplinary care is needed to truly optimize patient care.
Background:For patients with persistent atrial fibrillation (AF), pulmonary vein isolation (PVI) constitutes one of the main ablative procedure, but whether further left atrial (LA) substrate modification can optimize prognosis remains unclear. The purpose of the study efficacy and safety of Left Atrial substrate modification by Cryoballoon Ablation in persistent AF (LACA trial) is to clarify the efficacy and safety of PVI versus PVI plus LA substrate modification in persistent AF. Methods and design:This is a prospective, randomized controlled trial (RCT). Two hundred and fifty-six patients with persistent AF undergoing initial cryoballoon ablation will be randomly assigned in a 1:1 ratio to PVI alone or PVI plus LA substrate modification. The primary endpoint is the occurrence rate of atrial tachyarrhythmias (ATs) at 1 year after procedure. Secondary endpoints included safety of procedure, arrhythmia events during the blank period, quality of life assessment, thromboembolism, severe bleeding, cardiovascular death, and all-cause death. This is a prospective RCT designed to clarify the outcomes of PVI versus PVI plus LA substrate modification by cryoballoon ablation in persistent AF.Expected Outcomes:We hypothesize that, compared with PVI, the addition of LA substrate modification to PVI will lead to a lower rate of AF recurrence. Conclusion:This study evaluates if adding LA substrate modification to PVI improves outcomes in persistent AF versus PVI alone. Results will guide therapy by assessing superiority in sustaining sinus rhythm. Trial registration site:http://www.chictr.org.cn/index.aspx.Registration number:ChiCTR2200065626.
Background: The type of dietary fat may affect blood lipids and/or contribute to obesity, which can lead to various diseases. Elevated levels of triglycerides (TGs), low-density lipoproteins (LDL-Cs), total cholesterol (TC), or a combination of all three are known as hyperlipidemia. This study examined the effects of milk ghee (MG) and hydrogenated palm oil (HPO) on plasma lipids and white adipose tissue, considered as indicators of obesity in rats. Methods: Two groups of albino rats were fed diets containing different types of fat for eight weeks, with each group containing six male rats. Results: Rats fed HPO had substantially higher levels of high-density lipoproteins (HDL-Cs) than rats fed MG (56.33 and 51.66 mg/dL). The MG group had significantly high levels of TC, LDL-C, and TG (86.4, 34.73, and 56.20 mg/dL), and the HPO group had levels equal to 81.14, 24.80, and 47.13 mg/dL. White adipose tissue weight was significantly lower in rats fed HPO than in the MG group, and had smaller adipose cells. Conclusion: The intake of HPO could improve plasma lipids and obesity better than milk ghee.
Objective: To explore older patients’ perspectives on the acceptability and feasibility of a music intervention to reduce preoperative anxiety (PA) before cardiac surgery or Transcatheter Aortic Valve Implantation (TAVI). Methods: A monocentric, single-arm study was conducted between December 2023 and April 2024, involving patients aged 60 years or older undergoing cardiac surgery or TAVI. Each participant received a 20–30-minute music intervention session on the day before and the day of surgery. Music playlist was tailored to each patient’s preferred genres and specific music selections. Primary outcomes were patients’ acceptability and feasibility, evaluated through the consent rate, compliance rate and a postoperative interview. PA was measured using validated instruments. Results: Of 134 patients approached, 78 (58.2%) consented. Recruitment and follow-up were completed as planned. Music intervention was delivered to 71 patients, with 7 unable to participate for practical reasons. Compliance rates were 98.6% for the first session (n = 70) and 87.3% for the second session (n = 62). Interviews from 63 patients revealed high satisfaction, with 62 (98.4%) satisfied with the intervention, 57 (90.5%) interested in future music interventions, 58 (92.1%) liking the music, and 61 (96.8%) willing to recommend it to others. Approximately half of the participants (47.6%–66.7%) endorsed the key components of music intervention. Significant reductions in instrument-measured PA were observed after the first session, with 84.5% feeling relaxed immediately afterwards. Although reductions were not statistically significant after the second session, 91.1% felt relaxed immediately afterwards. No adverse events were reported. Conclusion: Music intervention is acceptable and feasible from the perspective of older patients undergoing cardiac surgery or TAVI. The observed immediate effect on PA should be considered as exploratory given the absence of a comparison group.
Background: The progressive decline in intrinsic capacity represents a major challenge in aging societies, yet its underlying inflammatory mechanisms remain poorly understood. This two-sample Mendelian randomization (MR) study aimed to investigate the causal relationships between 91 circulating inflammatory cytokines and five intrinsic capacity domains—locomotion, vitality, cognition, psychology, and sensory function. Methods: Genetic instruments for inflammatory cytokines were obtained from a large genome-wide association study involving 14,824 European participants. The primary causal estimates were obtained using the inverse variance-weighted (IVW) method, with sensitivity analyses performed using the MR-Egger and weighted median approaches. Results: Thirty-one cytokines were significantly associated with at least one intrinsic capacity domain. Notably, interleukin-13 (IL-13), CD40 ligand, and IL-8 exhibited pleiotropic protective effects on cognition, vitality, and psychological health, while elevated C-C Motif chemokine ligand 11 levels were consistently linked to increased risk of abnormalities of gait and mobility (odds ratio [OR] = 1.266; 95% confidence interval [CI]: 1.027–1.560; P = 0.027) and increased anxiety (OR = 1.001; 95% CI: 1.000–1.003; P = 0.031). Conclusion: This study provides genetic evidence for cytokine-mediated regulation of intrinsic capacity and identifies potential therapeutic targets for mitigating intrinsic capacity decline. However, the present MR approach was restricted to European ancestry, functional validation through experimental and clinical studies is warranted.
Purpose: Recovery after exercise is a critical window for assessing cardiovascular regulation and medication effects. Because beta-blockers (BB) attenuate sympathetic activity, we hypothesized that hypertensive patients using BB would demonstrate greater hemodynamic attenuation during post-exercise recovery compared with those using angiotensin II receptor blockers (ARBs). Methods: Fifty adults with hypertension (19 on BB monotherapy and 31 on ARB monotherapy) underwent treadmill exercise testing with standardized blood pressure (BP) and heart rate (HR) measurements at rest, peak exercise, and throughout a 6-minute recovery period. Results: Baseline systolic blood pressure (SBP) was similar between groups (BB: 125 ± 2 mmHg vs. ARBs: 129 ± 2 mmHg, P = 0.2879). During recovery, BB users exhibited significantly lower SBP at all time points, including minute 6 (135 ± 10 vs. 143 ± 11 mmHg, P = 0.0157), with differences evident from minute 1 onward (P < 0.05 for all). The rate–pressure product at recovery minute 6 was also lower in the BB group (12,260 ± 732 vs. 14,500 ± 401 mmHg·beats/min, P = 0.0056). HR during recovery was consistently lower among BB users at minutes 1, 2, 4, and 6 (all P < 0.05), reflecting blunted sympathetic drive. Conclusions: Hypertensive patients treated with BB exhibit greater attenuation of cardiovascular stress during post-exercise recovery compared with those using ARBs. These findings support a medication-specific effect on recovery hemodynamics, likely mediated by sympathetic blockade, with potential implications for exercise testing interpretation and cardiovascular risk stratification.
Background: We investigated the predictive effects of four insulin resistance (IR) surrogate indices, namely homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride-glucose (TyG), metabolic score of insulin resistance (METS-IR), and estimated glucose disposal rate (eGDR), on the risk of death in adults with metabolic syndrome-like characteristics. Methods: We selected 11,841 individuals with metabolic syndrome-like characteristics from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2018. Tthe relationships between various IR surrogates and mortality were assessed through Cox proportional hazards regression. Results: Over a median follow-up period of 123 months, there were 1,742 cases of all-cause mortality and 479 instances of cardiovascular mortality. Compared with patients with eGDR ≤ 6.30, there was a significantly lower risk of all-cause mortality in the second, third and highest eGDR quartiles (adjusted hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.68–0.95, P = 0.010; adjusted HR: 0.68, 95% CI: 0.55–0.85, P < 0.001; adjusted HR: 0.62, 95% CI: 0.46–0.84, P = 0.002, respectively; P for trend < 0.001). The eGDR showed a stronger correlation with all-cause mortality than HOMA-IR, TyG, and METS-IR, particularly among individuals under 60 years old. Notably, the relationship between eGDR and mortality showed a significant interaction with age (P for interaction < 0.001). Survival analysis further corroborated this discrepancy. Conclusions: The eGDR exhibited a more pronounced association with all-cause mortality among US adults presenting with metabolic syndrome-like characteristics, in comparison to the other three indices, particularly among individuals younger than 60 years.
Aneurysmal dilatation of the sinus of Valsalva is a rare clinical condition with diverse and serious complications. We report a unique case of a left sinus of Valsalva aneurysm (SOVA) causing coronary compression and ischemia, followed by an embolic stroke. A 73-year-old man presented with exertional chest pain. Computed tomography angiography revealed a large left SOVA compressing the coronary arteries. During hospitalization, the patient experienced recurrent embolic events and ultimately died before aneurysm repair. This case highlights the diagnostic challenge of SOVA and underscores the importance of early imaging and timely surgical intervention.
Background: Although the metabolic health benefits of Glucagon-like peptide-1 (GLP-1) medicines such as Wegovy and Zepbound are well-established, the potential effects of these medicines on psychiatric and mental health symptoms remain relatively unknown, particularly in higher-risk populations. The objectives of this study are to evaluate six-month changes in (1) psychiatric symptoms (e.g., depression, suicidality, posttraumatic stress, psychological distress); (2) eating disorders (e.g., binge eating, body image, weight-related stigma); and (3) health behaviors (e.g., pain interference, social support, sleep) in a sample of veterans receiving either semaglutide or tirzepatide as part of treatment for obesity in a multidisciplinary Department of Veterans Affairs weight management clinic. Methods: The study design consisted of a respective clinical trial. Participants were military veterans receiving GLP-1 treatment for obesity through a specialized weight control clinic. Veterans were asked to complete an anonymous online survey using validated psychological questionnaires to evaluate mental health symptoms at the beginning of and following 6-months of GLP-1 treatment. Results: Among 90 participants completing a pre-treatment survey, 40 also completed a post-treatment survey after six months of GLP-1 treatment. Weight loss averaged 13.1% over this period. We observed statistically significant changes in psychiatric, eating behavior, and health behaviors across outcomes including depressive symptoms, general mental health, sleep quality, eating behaviors, and pain interference (all P’s < 0.05). Effect sizes (Cohen’s d values) for these outcomes were moderate in magnitude by conventional standards (d ≥ 0.50). Conclusions: These results suggest that weight and metabolic health benefits experienced by patients may frequently be paralleled by statistically significant improvements in mental health, eating disorder symptoms, and health-related quality of life.
Background: Recent studies have suggested an association between height and heart failure (HF), yet findings have been inconsistent. To clarify this relationship, we utilized Mendelian randomization (MR) to investigate the potential causal link between height and HF. Methods: Independent single nucleotide polymorphisms (SNPs) associated with height were identified from genome-wide association studies data and used as instrumental variables. A two-sample MR approach was employed to explore the causal relationship between height and HF. For MR estimation, methods including inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode were utilized. The stability and reliability of the results were assessed using Cochran’s Q statistic, MR-Egger intercept test, and the leave-one-out method. Additionally, multivariate Mendelian randomization (MVMR) analysis was conducted to determine if height had an independent effect on HF, adjusting for potential confounders such as body mass index, blood sugar, blood pressure, blood lipids, smoking and drinking habits, coffee intake, and physical activity. Results: The two-sample MR analysis demonstrated a significant causal association between genetically predicted height and the risk of HF. Using the IVW method, a one-standard deviation increase in genetically predicted height was associated with a 6% higher risk of HF (95% confidence interval [CI] = 1.01–1.13, P = 0.03). This suggests that height is a significant risk factor. Evidence from SNP heterogeneity was noted ( P < 0.001), with no indication of horizontal pleiotropy ( P = 0.32). Re-evaluation using a random effects model confirmed the positive causal relationship between height and HF ( P = 0.03), unaffected by heterogeneity. Further, after adjusting for confounding factors in the MVMR analysis, height continued to show an adverse effect on HF (odds ratio = 1.11, 95% CI = 1.03–1.16, P < 0.01). Conclusions: This study establishes a causal relationship between height and HF, indicating that for every one-unit increase in height, the risk of HF increases by 11.1%.
Abstract Takotsubo syndrome (TTS) is an acute cardiac condition that primarily affects postmenopausal women and is often triggered by intense emotional or physical stress. TTS mimics acute coronary syndrome in its clinical presentation, with symptoms such as chest pain, dyspnea, and changes in the electrocardiogram and with the characteristic transient wall motion abnormalities that occur in the absence of culprit coronary artery disease. However, it is distinguished by the absence of significant blockage in the coronary arteries. The pathophysiology of TTS is not fully understood: It is believed to involve a surge in catecholamines leading to myocardial stunning. Psychological stress and psychiatric disorders are significant precipitating factors, emphasizing the importance of integrating psychological interventions in the treatment of TTS. Among various psychological approaches, mindfulness-based interventions (MBIs) have attracted attention for their role in contributing to cardiovascular health. Empirical evidence and recent neuroimaging studies support the effectiveness of MBIs in reducing stress, enhancing emotional regulation, and improving cardiovascular outcomes. There is evidence suggesting that MBIs could be a valuable complement to traditional medical treatments in TTS, potentially improving patient prognosis and quality of life. This review aims to examine the role of stress and psychiatric symptoms in the development of TTS and to assess the potential advantages of psychological interventions, such as mindfulness, in the treatment and prevention of this syndrome. Future studies should focus on long-term effects and optimal implementation strategies to maximize the benefits of mindfulness in managing TTS.
Cardiovascular (CV) disease (CVD) remains a leading cause of morbidity and mortality worldwide, with growing evidence highlighting the role of diet and the gut microbiome in cardiovascular health (CVH). This review synthesizes the current knowledge on the interactions between dietary patterns, the gut microbiome, and CV outcomes. High-fiber diets, such as the Mediterranean and Dietary Approaches to Stop Hypertension, promote beneficial microbial species, enhancing the production of short-chain fatty acids that exhibit anti-inflammatory and cardioprotective effects. Conversely, Western diets high in fat and low in fiber are associated with microbial dysbiosis and elevated trimethylamine-N-oxide (TMAO) levels, a metabolite linked to increased atherosclerosis and CVD risk. TMAO has been shown to amplify systemic inflammation by upregulating pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha, exacerbating CV damage. This review explores how microbiome composition influences metabolic and immune functions, contributing to systemic inflammation and endothelial dysfunction, which are critical in CVD progression. Personalized nutrition, informed by microbiome profiling, represents a promising avenue for optimizing CVH. Emerging therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation, also offer the potential for modulating the microbiome to improve CV outcomes.
Abstract Stress-induced cardiomyopathy is a multifaceted disease with a complex pathophysiology that not only affects the cardiovascular system but also the neuroendocrine systems and the psychological sphere of human beings. Excess catecholamines and hyperactivation of the sympathetic nervous system play a central role in myocardial function and microvascular integrity. There is increasing evidence that altered β-adrenergic receptors, oxidative stress, and endothelial dysfunction are involved in the pathogenesis of the disease. The possible genetic predisposition and the complex interplay between the cardiovascular and neuroendocrine systems are also still under investigation. Our review aims to summarize the established knowledge of stress-induced cardiomyopathy and highlight recent findings to provide a comprehensive overview of the pathophysiologic mechanisms and identify areas where further research is needed to expand our understanding and improve patient management.
Abstract As survival rates for cancer patients improve due to advancements in treatment modalities, there is an increasing prevalence of cardiovascular complications, necessitating a comprehensive understanding of this intersection. This review aims to elucidate the intricate relationship between cancer and cardiovascular disease, highlighting the growing concern of cardiovascular toxicity associated with cancer therapies. It explores various cancer treatments, including chemotherapy, targeted therapies, and radiation, and their associated cardiovascular risks, such as heart failure and ischemic heart disease. In addition, it discusses the importance of proactive cardiovascular risk assessments and ongoing monitoring in cancer patients to mitigate adverse outcomes. Strategies for prevention and management, including lifestyle modifications and pharmacologic interventions, are also examined to support the cardiovascular health of cancer survivors. Unlike previous reviews, this work integrates insights from multidisciplinary collaborations, emphasizing underexplored mechanisms of cardiovascular toxicity and the role of innovative monitoring tools. It also highlights emerging therapeutic strategies tailored to mitigate these risks, providing a forward-looking perspective in this critical area of research. The need for a collaborative method that includes oncologists, cardiologists, and primary care providers is emphasized to ensure integrated care that addresses both cancer treatment and cardiovascular health. This review serves as a critical resource for healthcare professionals seeking to improve the long-term outcomes for cancer survivors by recognizing and managing cardiovascular risks.
Abstract Cancer-related pain is a pervasive and debilitating symptom for many patients, often requiring effective management strategies to improve the quality of life and complement anti-tumor therapies. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed in cancer pain management as part of the World Health Organization’s three-step pain ladder. While NSAIDs are effective in controlling pain and inflammation, their long-term use in cancer patients raises concerns, particularly in the context of cardio-oncology and psycho-cardiology. NSAIDs, by inhibiting cyclooxygenase (COX-1 and COX-2) enzymes, can alleviate pain but also pose cardiovascular risks, such as increased risk of myocardial infarction and hypertension. These risks are exacerbated in patients with preexisting cardiovascular conditions or those undergoing cardiotoxic cancer treatments. Furthermore, the psychological toll of chronic cancer pain can exacerbate cardiovascular outcomes, creating a complex interplay between pain management, cardiovascular health, and psychological well-being. This review examines the role of NSAIDs in cancer pain management, highlighting the challenges posed by their cardiovascular and psychological implications. An integrated approach to pain management, considering both pharmacological and nonpharmacological strategies, is essential to optimize patient outcomes while minimizing risks.
Abstract As the number of transgender and gender-diverse (TGD) individuals seeking gender-affirming care continues to increase, it is crucial for healthcare providers to acknowledge the distinct challenges that this community faces and to offer personalized care. This article proposes a comprehensive review aimed at synthesizing current knowledge on the psycho-oncological challenges faced by TGD individuals. By exploring existing literature, it seeks to identify research gaps and provide a framework for addressing the intersection of gender identity, body image, and cancer-related healthcare needs. We aim to explore the complex relationship between being transgender and an oncologic patient, focusing primarily on the effects of gender-affirming hormone therapy (GAHT) and the implications of anatomical structures that remain after gender-affirming surgeries. The complex interplay between GAHT and cancer risks is highlighted, emphasizing the need for ongoing monitoring and tailored healthcare strategies. Psychological aspects of body image and self-identity among transgender individuals, particularly in the context of cancer treatment, are explored, as these treatments may involve significant bodily changes. For TGD individuals, these changes are intricately linked to their sense of identity and self-worth, leading to heightened distress and impaired quality of life. The disruption of sexual function due to cancer treatments can profoundly impact sexual identity and relationships, areas already vulnerable in the TGD population due to societal stigma. The role of social factors in shaping the experiences of TGD individuals in healthcare settings is also discussed, noting how these stressors can influence both the accessibility and quality of care. Research and clinical practice currently face gaps, and more comprehensive studies and guidelines that address the specific healthcare needs of TGD patients are warranted. The importance of an interdisciplinary approach, combining oncological care with gender-affirming practices, is underscored as essential for improving the overall health outcomes and quality of life for TGD individuals facing cancer.
Abstract Background: Heart failure (HF) is a leading cause of death in the United States (U. S.) and the world. HF is responsible for poor quality of life, frequent hospitalization, and increased health care costs. Although treatments are available, medication adherence is essential. Previous research has explored interventions to increase adherence for HF patients, yet barriers to medication adherence remain a challenge. This systematic review aims to examine the studies of adherence interventions among HF patients. The World Health Organization’s (WHO) model of Adherence to Long-Term Therapies, developed for patients with chronic illnesses, was the conceptual framework. The model groups barriers to adherence into five factors: patient-related factors, therapy-related factors, condition-related factors, social-economic factors, and health care team and health system factors. Methods: A search in databases CINAHL, PubMed, and Scopus identified intervention studies using the terms heart failure, medication adherence, and intervention. The inclusion criteria were that articles be the original reports of interventional studies exclusively with patients diagnosed with HF. Articles detailing only study protocols and interventions that did not measure medication adherence were excluded. Articles were categorized by setting, participant characteristics, adherence strategies, and design. Each article was evaluated using the Johns Hopkins guidelines for the level of evidence and quality. The WHO factor or factors addressed by each intervention and effectiveness in comparison to a control group were described. Results: A total of 40 articles met the inclusion criteria. All 40 addressed patient-related factors, 30 addressed therapy-related factors, 22 addressed condition-related factors, 26 addressed social-economic factors, and 22 addressed health care team and health system factors. Overall findings reinforced the WHO recommendation to support adherence by targeting the multiple factors at once. When examined individually, health care team and health system interventions had the greatest impact on increasing adherence. Limitations of this review include potential for bias, including the predominance of studies conducted in the U. S. and limited data collection by individual studies regarding race and ethnicity of the participants. Conclusions: Clinicians should incorporate a multidimensional approach when promoting adherence to medication regimens, with additional focus on the impact of the health care team and health system.
Background: Preterm neonates are highly susceptible to stress following their underdeveloped physiological systems and exposure to intensive medical interventions. Elevated blood cortisol levels and indicative of stress have been associated with adverse neurodevelopmental and physiological outcomes. Tactile-Kinesthetic Stimulation (TKS) and Soft Tissue Manipulation (STM) are non-invasive therapeutic interventions that may mitigate stress and promote overall development preterm neonates. This prospective experimental study aims to investigate effects of TKS and STM on blood cortisol levels in preterm neonates admitted to pediatric care settings. Methods: A total of 232 preterm neonates between 28 and 36 weeks of gestation will be randomly allocated into Intervention and Control group. The intervention group will receive TKS and STM twice daily for 24 minutes over 4 consecutive days, while the control group will receive standard care without additional interventions. Blood samples for cortisol levels will be collected on day 1 and day 4. Secondary outcomes comprise of physiological parameters (heart rate, oxygen saturation) and weight gain. Statistical analysis will compare baseline and post-intervention cortisol levels within and between groups. Expected Outcomes: We hypothesize that preterm neonates receiving TKS and STM to show significant reductions in blood cortisol levels and pain compared to the control group, alongside improved secondary outcomes. Conclusion: This study will provide evidence on the effectiveness of TKS and STM in reducing stress biomarkers, paving the way for integrating these interventions into neonatal care protocols to enhance the developmental trajectory of preterm infants.
