Randomized Study Research Articles

Efficacy of 15-minute music intervention on nursing students' anxiety, self-efficacy, and performance in simulation testing: A randomized study

BackgroundAnxiety can negatively impact nursing students' confidence and performance during simulation-based training, leading to suboptimal learning outcomes. SampleThe study included 102 prelicensure Bachelor of Science in Nursing (BSN) students. The participants (µage = 21.72, SD = 3.14), mostly female (n = 85, 83.33%) and Caucasian (n = 67, 65.69%), were randomized into control (n = 51) and experimental (n = 51) groups. MethodParticipants in the control group prepared for simulation as they usually would, while those in the experimental group listened to 15-minutes of classical music before their simulation sessions. Anxiety, self-efficacy, and instructor-assigned performance ratings during the simulation were evaluated. ResultsThe experimental group experienced significantly lower anxiety, increased self-efficacy, and higher performance scores compared to the control group (p-values < .001 for all measures). ConclusionThese results suggest that a 15-minute music-listening intervention could effectively reduce anxiety, boost self-efficacy, and improve performance during simulation-based training.

ASO Author Reflections: It Does Not Matter Whether Radical Prostatectomy is Performed in High-Risk Localized Disease or at the Oligometastatic Stage.

Radical prostatectomy (RP) alone has traditionally been considered insufficient for patients with high-risk localized prostate cancer (HRPC) owing to the frequent need for adjuvant salvage radiotherapy or androgen deprivation therapy (ADT) following surgery. Previously, systemic therapy, such as ADT, was the standard treatment for metastatic prostate cancer (PC) patients; RP was not considered viable for these patients. However, since 2015, there has been a recognition that metastatic PC patients can be categorized based on the extent of their metastases, leading to the consideration of RP for some metastatic cases. In recent years, the concept of cytoreductive RP has gained traction; studies suggest that it may improve survival rates in metastatic PC patients through mechanisms, such as tumor debulking and enhancement of the immune response. A meta-analysis of retrospective studies has shown that cytoreductive RP is associated with higher cancer-specific survival rates at 1-year, 3-year, and 5-year intervals compared with systemic therapy alone. In our study, which followed HRPC and oligometastatic PC patients for an average of 46 months, we observed biochemical recurrence in 17.8% of HRPC and 13% of oligometastatic patients, with overall survival rates of 96.4% and 87%, respectively. Although prospective or randomized studies are still lacking, current retrospective studies, including our own, suggest promising outcomes for RP in HRPC and oligometastatic patients. With the increasing prevalence of robotic surgery, improved pelvic anatomy observation, and growing surgical confidence, the realization of prospective randomized study results may not be far off.

In Vivo Imaging Techniques for the Human Scalp: A Systematic Review of the Literature.

Scalp inflammation and alopecia are distressing conditions for which patients regularly present to dermatology. Although some diagnoses can be made clinically, others require biopsy, which carries the risk of pain, infection, bleeding, and scarring. This review examines the existing literature regarding noninvasive in vivo imaging techniques and their evidence and utility in evaluating scalp pathology, with a focus on the diagnostics of hair conditions. A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines without timeframe restrictions. The PubMed and Clarivate (Web of Science) databases were searched using the terms ("imaging" OR "in-vivo imaging" OR "non-invasive imaging" OR "non-invasive in vivo imaging" "imaging," "in-vivo imaging) AND ("human scalp disorders" OR "scalp" OR "hair loss" OR "alopecia"). Peer-reviewed randomized control trials (RCTs), prospective studies, retrospective studies, and case series or reports discussing in vivo imaging of the scalp published before 2022 were selected. Forty-two studies were included and discussed; modalities included laser devices (n = 27), ultrasound (US) (n = 13), infrared thermography (n = 1), skin capacitance imaging (SCI), and ultraviolet light-enhanced visualization (ULEV) (n = 1). The most common laser devices used were reflectance confocal microscopy (RCM), multiphoton microscopy (MPM), and optical coherence tomography (OCT). US techniques included high-frequency US (HFUS) and US biomicroscopy (UBM). Quality imaging of the scalp in the setting of alopecic, neoplastic, and inflammatory diseases is highly sought after. Many of these noninvasive imaging techniques show promise, each with individual advantages and disadvantages in imaging-specific conditions. Ultimately, noninvasive imaging techniques may be used to optimize patient management and minimize morbidity associated with scalp biopsies.

Investigating the causal association between heme oxygenase-1 and asthma: A bidirectional two-sample Mendelian randomization analysis in a European population

BackgroundThe association between heme oxygenase-1 (HO-1) and asthma has been a subject of debate in both observational and experimental studies. We aimed to evaluate the potential causal relationship between HO-1 and asthma. Materials and methodsA bidirectional two-sample Mendelian randomization (TSMR) study was conducted to examine the causal relationship between HO-1 and asthma. In the forward Mendelian randomization (MR) analyses, HO-1 was considered as the exposure, while asthma as the outcome. Conversely, in the reverse MR analyses, asthma was regarded as the exposure, and HO-1 as the outcome. Data for HO-1 and asthma were obtained from publicly accessible genome-wide association studies (GWAS). These causal relationships were identified through 5 MR methods, namely MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode. Additionally, sensitivity tests were conducted to assess the robustness of MR study. Finally, additional asthma datasets and childhood asthma were selected to validate the findings. ResultsIn the forward MR analyses, according to the IVW method, genetically predicted HO-1 displays a negative correlation with the risk of asthma (OR 0.947, 95% CI 0.905–0.990). It was not found any SNP overly sensitive or disproportionately responsible for the outcome. No evidence of heterogeneity and pleiotropy between SNPs was observed. Genetically predicted asthma was not associated with HO-1 in reverse MR analyses using the IVW method. The same results were validated in additional asthma datasets and in childhood asthma. ConclusionThe results of MR analysis revealed heme oxygenase-1 as a protective factor for asthma.

Genetically Predicted Sleep Traits and Sensorineural Hearing Loss: A Mendelian Randomization Study.

Observational studies suggest a potential association between sleep characteristics, sensorineural hearing loss (SNHL), and sudden SNHL (SSNHL), but causal evidence is scarce. We sought to clarify this issue using two-sample Mendelian randomization analysis. The inverse-variance weighted (IVW) method was performed as primary analysis to assess bidirectional causal associations between sleep traits (chronotype, sleep duration, insomnia, daytime sleepiness, and snoring) and SNHL/SSNHL using publicly available Genome-Wide Association Studies summary data from two large consortia (UK Biobank and FinnGen). Sensitivity analyses, including Mendelian randomization (MR)-Egger, Mendelian randomization pleiotropy residual sum and outlier, weight median, Cochran's Q test, leave-one-out analysis, and potential pleiotropy analysis, were conducted to ensure robustness. IVW analysis found suggestive associations of morning chronotype (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.01-1.16, p = 0.031) and daytime sleepiness (OR = 1.88, 95% CI = 1.24-2.87, p = 0.003) with SNHL onset. Additionally, morning chronotype was nominally associated with SSNHL onset using IVW method (OR = 1.37, 95% CI = 1.10-1.71, p = 0.006). However, there was no evidence for the causal effect of SNHL and SSNHL on different sleep traits (all p > 0.05). Sensitivity analysis showed that the results were stable. Within the MR limitations, morning chronotype and daytime sleepiness were underlying causal contributors to the burden of SNHL, indicating that optimal sleep might facilitate the prevention and development of SNHL. 3 Laryngoscope, 134:4723-4729, 2024.

Association between cholelithiasis, cholecystectomy, and risk of breast and gynecological cancers: Evidence from meta-analysis and Mendelian randomization study.

Observational studies have shown that cholelithiasis and cholecystectomy are associated with the risk of breast cancer (BC) and gynecological cancers, but whether these relationships are causal has not been established and remains controversial. Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers. The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR]=1.04, 95% confidence interval [CI]: 1.01-1.06, p=0.002) and endometrial cancer (EC) (RR=1.26, 95% CI: 1.02-1.56, p=0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p=0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p=0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p>0.05). This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC.

The effect of depression status on osteoarthritis: A powerful two-step Mendelian randomization study.

There is no conclusive epidemiological evidence regarding the relationship between OA, depression, and whole-body fat mass. In this study, we conducted a two-step Mendelian randomization analysis to determine the causal relationships between them. The published summary-level data are from genome-wide association studies (GWAS). Our study included 357,957 samples and 10,828,862 SNPs. Finally, the outcome GWAS data for OA came from a GWAS on the genetic architecture of OA using UK Biobank data. This study included 50,508 samples and 15,845,511 SNPs. We used five different modes of analysis, including inverse variance weighted meta-analysis (IVW), MR-Egger regression, weighted median, simple mode, and weighted mode, to explore causal relationships. We found a positive correlation between depression and body fat mass, with depression leading to body fat mass an increase in (IVW result: p=3.39E-07, OR (95% CI) =2.16 (1.61, 2.90)). We also found a positive correlation between body fat mass and OA, with body fat mass increasing the risk of OA (IVW result: p=1.65E-33, OR (95% CI)=1.98 (1.77, 2.21). Body fat mass played an important role as a mediator in the causal relationship between depression and OA, with approximately 14% of the risk of OA caused by depression being mediated by body fat mass. Our study offers reliable evidence that depression has a detrimental impact on the risk of OA. Future research can support these associations from improving depressed effect, including social, biological, and behavioral factors, to reduce the risk of chronic diseases such as osteoarthritis. And we identified high-risk variation of alleles which associated with OA and depression can be used to predict disease and provide a basis for clinical intervention and treatment of OA.

The Causal Role of Thyroid Hormones in Bipolar Disorders: A Two-Sample Mendelian Randomization Study.

Bipolar disorder is a complex psychiatric condition with distinctions between clinical subtypes including Type 1 and 2 disorders. Several studies have proposed that thyroid hormones may be involved in the aetiology of bipolar disorders. This study employed a two-sample Mendelian randomization (MR) approach to investigate the causal relationships between six thyroid hormone metrics (TSH, FT4, FT3, TT3, FT3/FT4 and TT3/FT4) and bipolar disorder and Type 1 and 2 disorders, separately. Genome-wide association (GWAS) data from the ThyroidOmics Consortium (up to 271,040 individuals of European ancestry) were used for thyroid function metrics. Bipolar disorder GWAS data included 41,917 cases and 371,549 controls (25,060 Type 1 and 6,781 Type 2 cases). We applied inverse variance weighted (IVW) methods for primary MR analysis, with MR Egger, weighted median and weighted mode for sensitivity. Additional tests assessed horizontal pleiotropy and heterogeneity. Higher FT4 levels showed a protective causal effect against bipolar disorder (OR: 0.92, 95% CI: 0.86-0.97, p = 4.58 × 10-3) and a suggestive effect on Type 1 disorders (OR: 0.92, 95% CI: 0.86-0.99, p = 3.21 × 10-2). Elevated FT3 (OR: 1.18, 95% CI: 1.03-1.35, p = 1.55 × 10-2) and FT3/FT4 ratio (OR: 1.97, 95% CI: 1.02-3.82, p = 4.46 × 10-2) had suggestive harmful effects on Type 1 disorders. Sensitivity analyses showed consistent effects, with no significant horizontal pleiotropy or heterogeneity. These findings highlight the protective role of FT4 and the potentially harmful effect of elevated FT3 in Type 1 bipolar disorder, highlighting the need for further research on thyroid hormone levels as a potential treatment strategy for Type 1 bipolar disorder.

The impact of anxiety on the risk of kidney stone disease: Insights into eGFR-mediated effects.

Previous studies have linked kidney stone disease (KSD) with depression, but there are no reports on the relationship between anxiety and KSD, and the mechanism underlying the potential relationship remains unclear. Associations of anxiety and incident KSD were assessed in the National Health and Nutrition Examination Survey (NHENES) using multivariate logistic regression. Two-sample bidirectional Mendelian randomization studies and a two-step two-sample MR was used to estimate the mediating factors that influence KSD risk. Examinations of NHANES data revealed that a rise in the frequency and intensity of anxiety were independently associated with incident KSD. In MR analysis, anxiety (uk-a-51 and uk-b-6519) were from the UK Biobank, with sample sizes of 328,717 and 450,765 respectively. KSD data were from the FinnGen, including 8597 cases and 333,128 controls. In the IVW analysis, genetically predicted anxieties (ukb-a-51 and ukb-b-6519) were found to be causally associated with a higher risk of KSD, with odds ratios of 6.18 (95% CI 2.54-15.04) and 3.44 (95% CI 1.67-7.08), respectively. There were no reverse causal effects. Further mediation analysis indicated that anxiety increases the risk of KSD by raising eGFR, through which 11.8% of the effect of anxiety on KSD risk was mediated. The research was confined to individuals of European heritage, and there could be specific genetic variances among diverse ethnicities. The current study suggests anxiety as an independent causal risk factor for KSD and unveils a new pathogenic mechanism, showing that anxiety raises eGFR, thereby increasing the risk of KSD.

Exploring the Causal Relationship between Plasma Lipidome and Allergic Diseases: A Mendelian Randomization Study

Allergic diseases, including Allergic Rhinitis (AR), Allergic Asthma (AA), Allergic Conjunctivitis (AC), and Allergic Contact Dermatitis (ACD), affect a significant portion of the global population. Recent advances in lipidomics have highlighted the role of plasma lipids in immune regulation and inflammation.

Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study.

The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Mapping the evolving trend of research on leukocyte telomere length: a text-mining study

BackgroundSubstantial evidence indicates that measuring leukocyte telomere length (LTL) is a useful tool that may be considered as a valuable biomarker of individual biological age, correlating with numerous chronic disorders. However, to date, there has been a lack of in-depth understanding regarding the current landscape and forthcoming developments in the LTL field. Therefore, this study aimed to utilize bibliometric methods to summarize the knowledge structure, current focus, and emerging directions in this field.MethodScientific publications on LTL spanning the period from 2000 to 2022 were acquired from the Web of Science Core Collection database. Several bibliometric tools including CiteSpace, VOSviewer, and an online website were utilized for bibliometric analysis. The primary evaluations encompassed investigating the major contributors and their collaborative relationships among countries/regions, institutions, and authors, conducting co-citation analyses of authors, journals, as well as reference, examining reference bursts, as well as performing co-occurrence analyses of keywords.ResultsThere are 1818 papers with 66,668 citations identified. Both the annual publication and citation counts on LTL exhibited significant upward trends. The United States emerged as the most prominent contributor, as evidenced by the greatest volume of papers and the highest H-index value. University of California San Francisco and Aviv A were identified as the most productive institution and author in this domain, respectively. Reference analysis revealed that longitudinal study and mendelian randomization study are the most concerned research method in this field recently. Keywords analysis showed that the most concerned diseases in LTL fields were aging, inflammation, cardiovascular diseases, endocrine diseases, neurological and psychiatric diseases, and cancers. In addition, the following research directions such as “COPD”, “mendelian randomization”, “adiposity”, “colorectal cancer”, “National Health and Nutrition Examination Survey (NHNES)”, “telomerase reverse transcriptase”, “pregnancy” have garnered increasing attention in recent times and hold the potential to evolve into research foci in the foreseeable future.ConclusionThis is the first bibliometric study that provides comprehensive overview of LTL research. The findings of this study could become valuable references for investigators to explore and address the current and emerging challenges in LTL research.

Causal role of immune cells in muscle atrophy: mendelian randomization study

Immune system and inflammation had a great influence on the progression of muscle atrophy. However, the causal relationship with specific immune cell traits remained uncertain. The aim of this study was to elucidate the genetic influences on these associations, providing insights into the underlying mechanisms of muscle atrophy. A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between immune cell phenotypes and muscle atrophy. Data on immune cell phenotypes were obtained from a research cohort containing data on 731 immune cell phenotypes and data on muscle atrophy were sourced from a Finnish database. MR analysis was performed using the MR-Egger method, weighted median, inverse variance weighting, heterogeneity testing, sensitivity analysis, and multiplicity analysis, with results subjected to false discovery rate(FDR) correction. Additionally, the UK Biobank cohort was utilized as an external validation. A total of 31 immune phenotypes with causal relationships with muscle atrophy were identified, including various phenotypes of conventional dendritic cells, myeloid cells, T cells/B cells/natural killer cells, regulatory cells, and T cell maturation stages. Among them, 12 immune phenotypes were identified as exhibiting a positive causal relationship with muscle atrophy, while 19 immune phenotypes were demonstrated to have a negative causal association, highlighting the complex interactions between immune cells and muscle health. The results of the reverse MR analysis indicated that a negative correlation between muscle atrophy and CD28 on secreting Treg (OR = 0.9038, 95%CI:0.8308 ~ 0.9832, P = 0.0186). A significant positive correlation was revealed by external datasets between the CD25 on IgD + CD38- immune phenotype and the risk of muscle atrophy, which was consistent with the trend observed in the training group (OR = 1.1041, 95% CI: 1.1005–1.1076, P = 0.0263). No evidence of pleiotropy was observed, and the reliability of these findings was demonstrated by the leave-one-out analysis. The findings highlight significant correlations between certain immune cell features and muscle atrophy, providing potential targets for further investigation of immunological mechanisms and therapeutic interventions for this condition.

Exploring genetic links between blood metabolites and gout susceptibility.

Gout, a prevalent form of inflammatory arthritis, has a complex etiology where the causal relationship between metabolites and the disease remains underexplored. This study aims to elucidate the impact of genetically determined blood metabolites on gout. Employing a two-sample bidirectional Mendelian randomization analysis, we examined the association between 1400 blood metabolites and gout. Causal associations were determined using the inverse variance weighted (IVW) method with false discovery rate (FDR) correction. Sensitivity analyses encompassed weighted models, MR-Egger, weighted median, and MR-PRESSO approaches. MR-pleiotropy and Cochran's Q statistic were utilized to evaluate potential heterogeneity and pleiotropy. Additionally, metabolic pathway analyses were conducted to pinpoint relevant pathways. Of the initial 4 serum metabolites identified, 3 known metabolites-hexanoylglutamine levels, mannose content, and the phosphate to mannose ratio-were found to be causally associated with gout, along with 55 serum metabolites identified as potential predictors of gout (PIVW < 0.05). Furthermore, we discovered 3 metabolic pathways implicated in gouty attacks. Our findings, derived from Mendelian randomization, indicate that the identified metabolites and pathways may serve as biomarkers for clinical screening and prevention of gout. Additionally, they offer novel insights into the mechanisms of the disease and potential drug targets. Key points • Conducted a comprehensive Mendelian randomization study involving 1400 blood metabolites to explore their genetic impact on gout development and progression • Identified three key metabolites-hexanoylglutamine, mannose, and the phosphate-to-mannose ratio-with causal associations to gout, highlighting their potential use as biomarkers for early detection and risk stratification • Discovered 55 additional serum metabolites as potential predictors of gout, offering new insights into the pathophysiology of the disease and identifying high-risk individuals • Revealed three novel metabolic pathways involved in gout attacks, providing new therapeutic targets for precision medicine in gout treatment.

Implementation of sodium-glucose co-transporter 2 inhibitors in patients with heart failure through a new digital strategy (EMAIL-HF): a randomised clinical trial study design

Abstract Introduction Delayed implementation of new medical discoveries remains a global healthcare challenge and is mainly due to the complexity of cross-institutional patient care. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors is the latest medical discovery in heart failure (HF) and have recently been added to clinical guidelines as they have proven to reduce the risk of adverse cardiovascular outcomes in patients with HF across the ejection fraction spectrum. Whether a new digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients living with HF is of great importance for public health. Purpose To evaluate whether a new and streamlined digital strategy can optimise and accelerate the implementation of SGLT2 inhibitors in patients with HF. Design and methods: The trial is a multicentre, parallel group, register-based randomised clinical study, evaluating the effect and potential of a new digital strategy to implement new guideline therapies to patients living with a chronic disease, specifically SGLT2 inhibitors to patients with HF (figure 1). The setup employs data from nationwide health registers and official digital letters to inform patients about the new therapy option and invite them to have their eligibility evaluated by a HF specialist and start therapy. A total of ~10,000 patients with HF across the ejection fraction spectrum (with and without diabetes), who have not yet been started on SGLT2 inhibitors, are identified through Danish nationwide health registers, and randomised 1:1 to receive the digital letter (figure 2). The primary outcome is the proportion of patients redeeming a prescription of a SGLT2 inhibitor within six months. Secondary outcome is a composite HF endpoint consisting of all-cause death or HF hospitalisation. Other outcome measures are renal failure, stroke and myocardial infarction, safety outcomes, adherence to therapy and proportion of vulnerable patient groups initiating therapy including immigrants, elderly, frail patients, patients with lower socioeconomic level and lower educational level. A total of 4689 patients have been randomised (February 2024) and data will be presented in 2025. Conclusions The trial will determine the efficacy and safety of a new and streamlined digital strategy to implement SGLT2 inhibitors to patients with chronic HF. The setup has the potential to be used in a broad spectrum of patients living with chronic diseases and is expected to be highly cost-effective.Figure 1.Study hypothesisFigure 2.Study design

Mobile-Based Platform With a Low-Calorie Dietary Intervention Involving Prepackaged Food for Weight Loss for People With Overweight and Obesity in China: Half-Year Follow-Up Results of a Randomized Controlled Trial.

Obesity is a rapidly increasing health problem in China, causing massive economic and health losses annually. Many techniques have emerged to help people with obesity better adhere to intervention programs and achieve their weight loss goals, including food replacement and internet-delivered weight loss consultations. Most studies on weight loss interventions mainly focused on the change in body weight or BMI; however, body fat, especially visceral fat mass, is considered the main pathogenic factor in obesity. In China, more reliable evidence is required on this topic. Moreover, it is unclear whether an integrated weight loss program combining food replacement products, mobile app-based platforms, and daily body composition monitoring using a wireless scale is useful and practical in China. In this 2-arm, parallel-designed, randomized study, we explored the effectiveness and safety of the Metawell (Weijian Technologies Inc) weight loss program in China, which combines prepackaged biscuits, a wireless scale, and a mobile app. Participants in the intervention group were guided to use food replacement products and a scale for weight loss and monitoring, whereas participants in the control group received printed material with a sample diet and face-to-face education on weight loss at enrollment. The intervention lasted for 3 months, and follow-up visits were conducted at months 3 and 6 after enrollment. Dual-energy x-ray absorptiometry and quantitative computed tomography were used to assess body fat. A multilevel model for repeated measurements was used to compare differences between the 2 groups. In total, 220 patients were randomly assigned to intervention (n=110) and control (n=110) groups. Participants in the intervention group had significantly greater decreases in BMI, total body fat, visceral adipose area, and subcutaneous adipose area (all P<.001) than those in the control group. However, the rate of change in lean mass was not significantly different between the 2 groups (P=.62). Further, 35 participants in the intervention group reported adverse events. Constipation was the most frequently reported adverse event (11/110), followed by dizziness (6/110), hypoglycemia (4/110), fatigue (3/110), and gastritis (3/35). The Metawell program was effective for weight loss. After the intervention, participants in the intervention group lost more body weight and body fat while retaining muscle mass than those in the control group.

Interleukin-6 signalling, lipoprotein (a) lowering and cardiovascular disease: a mendelian randomisation study

Abstract Background Elevated lipoprotein(a) (Lp[a]) levels and chronic low-grade inflammation play causal roles in cardiovascular disease (CVD) development, representing promising targets for managing residual risk. CVD prevention trials are currently assessing the efficacy of IL-6 pathway inhibition in ameliorating chronic pro-atherogenic inflammation. Lp(a) increases in response to interleukin 6 (IL-6) and acute inflammatory states, and Lp(a) itself induces an inflammatory response that accelerates atherosclerosis. Recent studies indicate that IL-6-receptor inhibitors may lower Lp(a) levels and reduce inflammation, potentially decreasing CVD risk in an additive manner. Purpose This drug-target Mendelian Randomisation (MR) study aims to elucidate the on-target effects of pharmacological IL-6R and LPA inhibition on CVD and explore the relationship between downregulated IL6R signalling and Lp(a) levels. Methods Independent genetic variants associated with C-reactive protein levels from around the IL6R gene locus, and Lp(a) lowering variants from around the LPA gene locus were utilised to assess the effect of genetically proxied IL6R and LPA inhibition on CVD risk in large genomic consortia. Two-step cis-MR was then employed to estimate the effect of lower genetically predicted IL6R signalling on CVD, after adjusting for its influence on Lp(a) levels. Results Genetically proxied LPA inhibition was associated with reduced odds of coronary artery disease (CAD) (OR 0.88, 95% CI 0.86-0.89), ischaemic stroke (IS) (OR 0.98, 95% CI 0.96-1.00), cardioembolic stroke (OR 0.95, 95% CI 0.92-0.97), heart failure (HF) (OR 0.96, 95% CI 0.92-1.00), and aortic stenosis (OR 0.88, 95% CI 0.85-0.91). IL6R inhibition was associated with reduced odds of CAD (OR 0.76, 95% CI 0.68-0.86), IS (OR 0.89, 95% CI 0.80-0.98), small vessel stroke (SVS) (OR 0.72, 95% CI 0.59-0.89), large artery stroke (LAS) (0.61, 95% CI 0.48-0.78) and atrial fibrillation (OR 0.73, 95% CI 0.65-0.83). Furthermore, downregulated IL6R signalling was associated with lower Lp(a) levels (SD change -0.04, 95% CI -0.08,-0.01). In two-step cis-MR, Lp(a) levels partially mediated the total effect of IL6R inhibition on CAD (proportion-mediated = -11.33%, 95% CI -11.35, -11.31%) and LAS (proportion mediated = -4.19%, 95% CI -4.21, -4.17%), but had little effect on IS (proportion-mediated = -1.78%, 95% CI -1.80, -1.76%), SVS (proportion-mediated = -2.50%, 95% CI -2.52, -2.48%), or atrial fibrillation (proportion-mediated = -0.20%, 95% CI -0.22, -0.18%). Conclusion IL6R and Lp(a) inhibition are independently associated with reduced risk of CVD. Furthermore, IL6R inhibition is associated with lower Lp(a) and its effect on CVD is independent of its Lp(a)-lowering effects. Targeting the IL6 signalling pathway offers a promising approach to mitigate residual CVD risk in individuals with elevated Lp(a) levels. Future trials should investigate the additive effects of combined IL-6 inhibition and Lp(a) lowering therapies.

Effect of sodium-glucose cotransporter-2 inhibitor (SGLT2-i) in patients with LVAD: a systematic review and meta-analysis

Abstract Introduction Sodium-glucose cotransporter-2 inhibitor (SGLT2-i) have been shown to reduce risks of clinical events in patients with heart failure (HF). However, data on the use of SGLT2-i in patients with left ventricular assist devices (LVAD) are scarce. We thought to assess the efficacy and safety of SGLT2-i in patients with LVAD Methods A systematic search was done in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to December 2023. We used all relevant words for "SGLT2-i" and "LVAD" to search in databases and we included studies and published abstracts in peer-reviewed journals of studies assessed SGLT2-i in patients with LVAD. The efficacy and safety data were extracted across the studies. RevMan 5.4.1 was used for meta-analysis. Results Three studies and eight abstracts totaling 209 patients using SGLT2-i were included. Empagliflozin, Dapagliflozin, and Canagliflozin were the used SGLT2-i across the included studies. SGLT2-i effectively decreased hemoglobin A1c (HbA1c) (Mean = -0.44, 95% CI [-0.79, -0.09], p = 0.01) and diuretic dose (Mean=-2.54, 95% CI [-3.56, 1.51], p&amp;lt; 0.00001) from baseline. No significant improvement was found for glomerular filtration rate (GFR), B-type natriuretic peptide (BNP), or mean pulmonary artery pressure (MPAP). Regarding safety, the pooled percentage of people with driveline infection was 9.33%, 95% CI [2.05, 16.60], p=0.01. Conclusion SGLT2-i effectively improves HbA1c and diuretic dose in patients using LVAD. Further randomized studies with a large number of participants may be warranted.

Strategy optimization for the combined procedure of left atrial appendage occlusion plus catheter ablation in patients with atrial fibrillation (COMBINATION): a multi-center, randomized study

Abstract Background The long-term efficacy and safety of combining left atrial appendage closure (LAAC) plus catheter ablation (CA) in patients with atrial fibrillation (AF) in a single procedure have been established. However, the optimal combining strategy has not been well elucidated. Objective To determine the impact of different combining strategies on long-term clinical outcomes. Methods In this prospective multicenter study, patients with non-valvular AF referred for the combining procedure were randomly assigned to the ablation-first or occlusion-first groups at a 1:1 ratio. We evaluated the outcomes of LAAC with a Watchman device and CA using a contact-force sensing catheter during long-term follow-up. Results Of the 202 randomized patients, 194(96.0%) completed the trial with 97 patients in each group. Baseline characteristics were comparable between groups. All procedures were accomplished with acute successful LAAC and restoration of sinus rhythm. Incidences of periprocedural complications were similar. Higher chronic peri-device leak (PDL, 15.5% vs 5.2%, P=0.031) and device-related thrombus (DRT, 8.2% vs 1.0%, P=0.035) rates were observed in the ablation-first group. The event-free survival rate of the primary endpoint (composite of stroke/transient ischemic attack, thromboembolism, clinically-relevant bleeding, cardiovascular rehospitalization/death) was significantly higher in the occlusion-first group (83.5% vs 71.1%, log-rank P=0.036, HR 0.53, 95%CI 0.29-0.95) during a median 2.5-year follow-up. Patients with male gender and higher CHA2DS2-VASc score were at lower risk in the subgroup analysis. Long-term freedoms from AF (77.3% vs 63.5%, log-rank P=0.039) and atrial tachyarrhythmias (70.1% vs 55.7%, log-rank P=0.044) were higher in the occlusion-first group, respectively. Conclusions The occlusion-first approach is recommended for combined procedures where a plug-like device is implanted due to its superior long-term clinical benefits.Flowchart of the COMBINATION trialIncidences of primary endpoint

Transcriptome-wide Mendelian randomization during CD4+ T cell activation reveals immune-related drug targets for cardiometabolic diseases

Immunity has shown potentials in informing drug development for cardiometabolic diseases, such as type 2 diabetes (T2D) and coronary artery disease (CAD). Here, we performed a transcriptome-wide Mendelian randomization (MR) study to estimate the putative causal effects of 11,021 gene expression profiles during CD4+ T cells activation on the development of T2D and CAD. Robust MR and colocalization evidence was observed for 162 genes altering T2D risk and 80 genes altering CAD risk, with 12% and 16% respectively demonstrating CD4+ T cell specificity. We observed temporal causal patterns during T cell activation in 69 gene-T2D pairs and 34 gene-CAD pairs. These genes were eight times more likely to show robust genetic evidence. We further identified 25 genes that were targets for drugs under clinical investigation, including LIPA and GCK. This study provides evidence to support immune-to-metabolic disease connections, and prioritises immune-mediated drug targets for cardiometabolic diseases.