Statistical Power Research Articles

Evidence for the association between rheumatoid arthritis (RA) and osteoporosis (OP) remains inconsistent, and the role of inflammatory cytokines in mediating this association remains unclear. This study used linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), and colocalization analyses to assess the association between RA and OP. Mediation MR analysis was conducted to explore the mediating role of inflammatory cytokines. Multitrait analysis of GWAS enhanced statistical power and identified novel genetic associations. Independent risk loci were examined using GCTA-COJO, PLACO, and FUMA analyses. Risk-associated genes were identified by integrated MAGMA, SMR, and TWAS methods, while BLISS analysis revealed relevant proteins. The GEO database was used to validate pleiotropic gene expression. Genetic correlation (rg = 0.171), causal association (OR = 1.103), and colocalization analysis (PPH4 = 0.99) together confirmed a genetic link between RA and OP. Interleukin (IL)-17 mediated the RA-OP association. The SNPs rs11574914 and rs11889341 are MTAG-RA independent risk loci. Twenty-five RA-related risk genes are specifically expressed in the lymph node and tonsils. FCRL3 regulates the RA immune infiltration microenvironment. IL-17 promotes the progression of RA to OP; FCRL3 regulates the immune infiltration microenvironment of RA and is a potential therapeutic target. Key Points • Genetic correlation, MR, and colocalization analyses confirm a shared genetic basis between RA and OP. •IL-17 is identified as a key inflammatory mediator driving the progression from RA to OP. •Multi-trait GWAS and integrative post-GWAS analyses uncover novel RA-specific loci and 25 immune-related risk genes. •FCRL3 regulates immune cell infiltration in RA and emerges as a potential therapeutic target for inflammation-induced bone loss.

Background: With the evolving legal landscape in South Africa, cannabidiol (CBD) and non-medical cannabis products are increasingly available, posing challenges for healthcare professionals. Retail pharmacists, as key figures in patient care, face a critical knowledge gap in providing informed advice on these products. This study assessed the attitudes and clinical knowledge of retail pharmacists in South Africa regarding the recommendation and patient counselling with respect to CBD and non-medical cannabis. Methods: A cross-sectional quantitative design study was conducted, using an online survey to evaluate pharmacists’ knowledge and attitudes towards CBD and non-medical cannabis. A sample of 178 pharmacists provided a statistical power of 0.997, ensuring robust results. Results: While 69% of pharmacists recognised CBD’s therapeutic potential, 63% felt unprepared to recommend it because of insufficient knowledge and 60% cited a lack of resources in their pharmacies. Only 13% scored above 50% in the knowledge assessment, which included legislative and clinical understanding related to CBD and non-medical cannabis, with 31% reporting no formal training to educate themselves on CBD products. Conclusion: This study highlights the need for targeted educational initiatives and clear South African Health Products Regulatory Authority (SAHPRA) guidelines to bridge knowledge gaps among retail pharmacists. Updated resources on CBD safety, interactions and therapeutic use are critical to empower pharmacists to deliver evidence-based counselling. Contribution: The findings contribute to healthcare education, policy reform, and health promotion by emphasising the importance of equipping pharmacists with the tools necessary for safe and effective counselling on CBD and cannabis products.

Investigating retention time and fluid dynamics of the vehicles in non-invasive topical ocular drug delivery systems.

Prolonged prone positioning (PPP) for ≥ 24h may enhance outcomes in moderate to severe acute respiratory distress syndrome (ARDS), but may also increase risks such as pressure injuries and complications. Despite clinical rationale, high-quality evidence for PPP's safety and efficacy remains scarce. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) and observational studies. Trials that compared two distinct treatment groups in adult patients with ARDS were included: prone position < 24h (standard) and ≥ 24h (prolonged). Databases searched included MEDLINE, CENTRAL, ClinicalTrials.gov, ISRCTN, ICTRP and the Cochrane Covid-19 Study Register (last search: 3 July 2025). Risk of bias was assessed using ROB-2 for RCTs, and the ROBINS-I V2 tool for non-randomised intervention studies (NRSI). The primary outcome was mortality. Secondary outcomes included improvement of oxygenation and adverse events. Outcomes (Risk ratios and hazard ratios) were calculated using a random-effect model with 95% confidence intervals (CI). The quality of evidence was evaluated using the GRADE assessment. Of 19,986 records, 9 (n = 1,045) were included in the qualitative and quantitative analysis. Four studies, including two small RCTs (n = 112) and two NRSIs (n = 581), had a low to moderate risk of bias. Most studies included patients with COVID-19 ARDS. Meta-analysis showed no significant effect on 90-day mortality (n = 641, HR 0.72; 95% CI 0.41-1.25). No heterogeneity was detected among studies (I² = 0%), but the confidence interval for I² was wide (95% CI: 0-89%), suggesting the possibility that substantial heterogeneity may exist. Similarly, no significant differences were found for secondary outcomes. Current evidence does not support the use of PPP outside of clinical studies. Pooled data from small trials and NRSIs reveal no significant effect of PPP on mortality, oxygenation, or safety outcomes. The evidence is of low to very low certainty, limited by inconsistency and imprecision. The wide confidence intervals indicate low statistical power, therefore both harm and benefit remain plausible on the basis of the available evidence. Well-powered RCTs are needed to clarify the potential benefits and risks of PPP in ARDS.

Does the interaction between CFTR and AQP7 in human spermatozoa play a role in the molecular mechanisms underlying sperm motility? CFTR inhibition reduces sperm motility and AQP7-mediated glycerol permeability in human spermatozoa, and CFTR and AQP7 co-localize in the equatorial segment of the sperm head, with in silico modeling suggesting a potential interaction between these proteins. CFTR modulates the permeability of aquaglyceroporins in multiple tissues, and their interaction is mediated by the scaffolding protein NHERF1. AQP7-mediated glycerol permeability correlates with sperm motility. Semen samples were collected from normozoospermic men (normal motility; n = 33) and men with asthenozoospermia (reduced motility; n = 15) at a fertility clinic between September 2020 and January 2021. Isolated sperm from men with normozoospermia were used to study the effect of CFTR on sperm motility (N = 10) and glycerol permeability (N = 23). Sperm from 14 asthenozoospermic samples and 13 normozoospermic samples were used to compare the effect of CFTR on AQP7-mediated glycerol permeability, after screening for the absence of common CFTR gene variants. Sperm membrane permeability to glycerol was measured using stopped-flow light scattering, and the effect of CFTR conductance was modulated using a specific inhibitor (CFTRinh172). The interaction between CFTR and AQP7 was investigated using co-immunofluorescence, proximity ligation assay, and in silico approaches like ColabFold and GROMACS. Gaussian distribution of the data was measured by the Shapiro-Wilk normality test. Data showing non-normal distribution was treated with the Kruskal-Wallis test, whereas normal distribution data were treated with an ordinary one-way ANOVA. Comparisons between normozoospermic and asthenozoospermic groups were performed using an unpaired two-tailed Mann-Whitney U test. A P-value less than 0.05 was considered significantly different. CFTR inhibition negatively affected sperm motility (0.53 ± 0.11-fold variation to control, P < 0.05) and AQP7-mediated glycerol permeability (0.459-fold [0.314; 0.537] variation to control, P < 0.01). Despite this, the effect of CFTR dysfunction on AQP7-mediated glycerol permeability of sperm from normo- versus asthenozoospermic samples did not reach statistical significance (P = 0.068) due to low statistical power, but a tendency was apparent. A larger sample size is needed to confirm this trend. CFTR and AQP7 (the main glycerol diffuser in human sperm) co-localize and are in proximity in the midpiece and in the equatorial section of the sperm head in human sperm. In silico analysis supports the interaction of CFTR with AQP7 intermediated by NHERF1, indicating a mechanism of physical modulation of AQP7 permeability by CFTR. Only cystic fibrosis-associated CFTR variants were screened during this study; the presence of assumed benign variants that could slightly decrease CFTR function may have impacted the results. Glycerol permeability was measured indirectly by assuming its proportionality with the change in sperm volume through time after the osmotic shock. A larger sample size would be needed to confirm the trends that did not reach statistical significance. Furthermore, pharmacological assays were conducted in a non-nutrient buffer to specify direct effects of the channel; this condition differs from physiological media and represents a specific limitation of this study. Our findings suggest that a novel mechanism based on the functional and physical interaction between CFTR and AQP7 may underlie some cases of asthenozoospermia and idiopathic male infertility; the results also increase our knowledge of the molecular mechanisms governing sperm motility. This research was funded by Fundação para a Ciência e a Tecnologia (FCT) to UMIB (UIDB/00215/2020, and UIDP/00215/2020), ITR-Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020), and the post-graduate student João C. Ribeiro (UI/BD/150749/2020). The work was co-funded by FEDER through the COMPETE/QREN, FSE/POPH, and POCI-COMPETE 2020 (POCI-01-0145-FEDER-007491) funds. P.F.O. is funded by national funds through FCT, I.P., under the Scientific Employment Stimulus-Institutional Call-reference CEEC-INST/00026/2018. This work also received support and help from FCT/MCTES to LAQV-REQUIMTE (LA/P/0008/202-DOI 10.54499/LA/P/0008/2020, UIDP/50006/2020-DOI 10.54499/UIDP/50006/2020, and UIDB/50006/2020-DOI 10.54499/UIDB/50006/2020) and to iBiMed (UIDB/04501/2020-DOI 10.54499/UIDB/04501/2020 and UIDP/04501/2020-DOI 10.54499/UIDP/04501/2020), through national funds. There are no conflicts of interest to declare. N/A.

The current study used a culture-independent methodology to investigate the rumen microbiome composition in two genetically divergent groups of spring-calving dairy cows, high (€218) and low (€157) Economic Breeding Index (EBI), grazing two sward treatments—perennial ryegrass (grass-only) or perennial ryegrass and white clover (grass-clover)—at three time points across spring, summer, and autumn of a single grazing season. The analysis indicated that the EBI status had no significant effect on the rumen microbial community within the statistical power of this study. Beta diversity between the microbiomes was different ( p &amp;lt; 0.001) between the two sward treatments only in autumn, when the clover proportion was highest (50.2%). Season had a significant effect on microbiome beta diversity across sward treatments ( p &amp;lt; 0.001). There were only minor differences in the composition of the rumen microbiomes between the two sward treatments. Many bacterial genera were differentially abundant between spring and the two later time points. Bacterial genera that were more abundant in spring were positively correlated with rumen propionate levels, while those more abundant in summer and autumn were negatively correlated with propionate and positively correlated with acetate and butyrate. Methanogenic archaeal abundance was greater in summer and autumn compared to spring, and they were negatively correlated with propionate and positively correlated with methane (CH 4 ) production. The results of this study demonstrate that genetic selection using the EBI does not affect the rumen microbial community and the core rumen microbial community is similar in cows grazing either grass-only or grass-clover swards. The results also demonstrate that the rumen bacterial community shifts across the grazing season, providing more favorable conditions for methanogenesis in summer and autumn compared to spring.

Information borrowing from historical data is gaining increasing attention in clinical trials for rare and pediatric diseases, where small sample sizes may lead to insufficient statistical power for confirming efficacy. While Bayesian information borrowing methods are well established, recent frequentist approaches, such as the test-then-pool and equivalence-based test-then-pool methods, have been proposed to determine whether historical data should be incorporated into statistical hypothesis testing. Depending on the outcome of these hypothesis tests, historical data may or may not be utilized. This paper introduces a dynamic borrowing method for leveraging historical information based on the similarity between current and historical data. Similar to Bayesian dynamic borrowing, our proposed method adjusts the degree of information borrowing dynamically, ranging from 0 to 100 %. We present two approaches to measure similarity: one using the density function of the t-distribution and the other employing a logistic function. The performance of the proposed methods is evaluated through Monte Carlo simulations. Additionally, we demonstrate the utility of dynamic information borrowing by reanalyzing data from an actual clinical trial.

To explore the relationship between migraine attack onset in children and adolescents and Chinooks, which are dry and warm westerly winds that generally occur in the winter and bring about abrupt weather changes to the east of the Rocky Mountains in Southern Alberta, Canada. This was a prospective longitudinal clinical cohort study with recruitment from November 2020 to May 2024. Participants were: 8-18 years old, had migraine as per International Classification of Headache Disorders 3rd edition criteria, had 1-15 headache days/month, lived in the geographical location where Chinook winds occur, and had exposure to at least one pre-Chinook or Chinook day during the study period. Chinook days were defined using Nkemdirim's criteria and Environment Canada data were used to categorize day type as either Chinook, pre-Chinook, or non-Chinook. Weather data were merged with data from daily headache diaries, completed for periods of 8-30 days. The primary outcome was attack onset, defined as a day with a new migraine attack of moderate or severe severity, as per the 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). Both univariate and adjusted models were used to determine if there was an association between migraine attack onset and day type (i.e., pre-Chinook, Chinook, or non-Chinook) at the aggregate study sample level. The adjusted models controlled for age and sex, and both models included a random intercept. Subsequently, individual n = 1 models were fitted to explore each individual participant's personal odds of migraine attack onset on both pre-Chinook and Chinook days versus non-Chinook days. Pre-Chinook/Chinook sensitivity values were calculated for each individual by dividing the model's regression coefficient by its standard error. Sensitivity values >1.96 suggest a significant association between pre-Chinook/Chinook days and attack onset. Sixty youth with 1253 days of complete data, of which 144 (12%) were attack onset days, participated in the study. There were 158 Chinook (13%), 124 pre-Chinook (10%), and 971 non-Chinook days (77%). There were 39 female participants (39 of 60; 65%), with a median age of 14 years (quartile [Q] 1 = 12, Q3 = 16), and a median headache frequency of 6.2 days/month (Q1 = 4, Q3 = 11). Neither the univariate nor the adjusted models found any significant association between day type and attack onset at an aggregate level (pre-Chinook adjusted odds ratio [OR], 0.98; 95% confidence interval [CI], 0.54-1.78, p = 0.947; Chinook adjusted OR, 1.15; 95% CI, 0.69-1.91, p = 0.596). No individual participants met the threshold for statistically significant pre-Chinook or Chinook sensitivity. We did not find a relationship between pre-Chinook and Chinook conditions and migraine attack onset. This may be due to the lack of an association between Chinooks and attack onset in youth with migraine, or due to a lack of statistical power in our study. Future studies with greater statistical power should aim to assess for a potential relationship between Chinooks and attack onset, as it could have important treatment implications.

Background/Objectives: Children who have received hematopoietic cell transplants (HCTs) often face complex clinical courses and complications that increase their risk of functional impairments. Because of this, pediatric HCT recipients may benefit from early mobilization efforts to reduce long-term functional issues. However, early ambulation can be limited by clinical complexity and concerns about infectious transmission in HCT patients. Some patients are under contact precautions due to colonization with bacteria that produce extended-spectrum beta-lactamase (ESBL) enzymes. Our goal was to significantly increase ambulation in pediatric HCT recipients at our institution within three months of the intervention. We aimed to raise the number of ambulation events per day, the number of physical therapy (PT) visits per week, and the distance patients walked with PT per session. Methods: From January to October 2022, data on mobilization, demographics, and clinical characteristics were retrospectively collected from electronic health records. Starting in June 2022, we permitted ESBL-colonized patients to leave their rooms while wearing personal protective equipment (PPE), and we trained clinical staff about this in our QI initiative. Results: In Group 1, the ambulation rate was 1.36 times higher before the intervention than after, with an effect size of 0.3042 (p = 0.004 *). The ambulation rate in Group 2, admitted before the intervention, was 1.33 times higher than in Group 3, admitted after the intervention, with an effect size of 0.2856 (p = 0.016 *). Conclusions: The initiative did not increase ambulation among the targeted group. Patients ambulated more before the intervention, though these results lack statistical power. The lack of success of the intervention may be due to various factors, including the short monitoring period, retrospective data collection, difficulties with PPE use among young patients, and uncollected confounding variables related to clinical status.

Atherosclerosis is a pathophysiological process common to a range of cardiovascular diseases. We reasoned that considering clinical presentations of atherosclerosis across the coronary, peripheral, and cerebrovasculature as a single entity would enhance statistical power to identify rare genetic variation driving pathological processes across multiple vascular beds. We performed an exome-wide association study of atherosclerotic cardiovascular disease in 434 438 UK Biobank participants of European ancestry. We identified rare, predicted damaging variants in HTRA1, SGTB (small glutamine-rich tetratricopeptide repeat co-chaperone beta), and RBM12 to be associated with risk of atherosclerotic cardiovascular disease, independent of known risk factors. Both SGTB and HTRA1 were downregulated in the aorta of patients with coronary artery disease compared with controls. Loss-of-function variants in the RNA-binding protein RBM12 increased the risk of coronary, cerebrovascular, and peripheral vascular diseases to a similar extent. SGTB increased the risk of atherosclerotic cardiovascular disease in the coronary and peripheral circulations but not the cerebrovasculature. While loss-of-function variants in HTRA1 are known to cause monogenic stroke syndromes, we found that damaging missense variants in HTRA1 are associated with increased risk of disease in both the cerebrovascular and coronary circulation. Surprisingly, the increased risk of coronary artery disease was driven predominantly by a single missense variant (p.R227W; minor allele frequency, 0.009). In vitro, the R227W mutant HTRA1 efficiently proteolyzed the disordered substrate casein but not aggregated α-synuclein. In contrast, a stroke risk-raising variant (D320N) could not efficiently process any of the tested substrates. We identified novel genetic variants predisposing to atherosclerotic cardiovascular diseases that act independently of established cardiovascular risk factors. The observed phenotypic and functional heterogeneities between HTRA1 variants suggest that distinct biochemical mechanisms drive HTRA1-related vascular disease in the brain and heart.

Background The impact of hypothyroidism, which can be divided into overt hypothyroidism and subclinical hypothyroidism, on severe postpartum hemorrhage (SPPH) remains unknown. Methods A total of 34,303 pregnant women from the Third Affiliated Hospital of Guangzhou Medical University between 2016 and 2020 were included in this retrospective cohort study. We employed three logistic regression models incorporating different covariates to explore the relationship between hypothyroidism and SPPH, followed by an interaction analysis to identify potential modifiers. Then, we performed a stratified analysis to examine the influence of potential modifiers on the association between hypothyroidism and SPPH. Finally, sensitivity analyses were conducted to evaluate the robustness of our findings. Results In the logistic regression analysis, we found that hypothyroidism was correlated with an elevated risk of SPPH (OR = 1.609, 95% CI: 1.111–2.329, p = 0.012). In addition, overt hypothyroidism had a significant impact on the increased risk of SPPH (OR = 1.688, 95% CI: 1.137–2.507, p = 0.009), whereas no significant association with SPPH was observed for subclinical hypothyroidism (OR = 1.208, 95% CI: 0.443–3.291, p = 0.712). In the relationship between hypothyroidism and SPPH, we observed that age and history of radiation exposure acted as potential modifiers ( p for interaction &amp;lt; 0.05). Additionally, the correlation between hypothyroidism and SPPH was stronger in pregnant women aged &amp;lt; 35 years (OR = 2.412, 95% CI: 1.583–3.673, p &amp;lt; 0.001) than in those aged ≥ 35 years (OR = 0.755, 95% CI: 0.364–1.567, p = 0.450). Conclusions Overt hypothyroidism had a significant impact on the elevated risk of SPPH, especially in pregnant women aged &amp;lt; 35 years. In contrast, subclinical hypothyroidism showed no significant association with SPPH, which may reflect limited statistical power rather than the absence of risk. These findings offer valuable insights into the relationship between hypothyroidism and SPPH, potentially optimizing maternal outcomes by preventing and intervening in the occurrence of SPPH.

Introduction: Catheter ablation is a commonly performed invasive procedure for management of atrial fibrillation (AF), and offers favorable cardiovascular outcomes and improved quality of life in patients with AF. However, it is associated with procedural complications. Reported complication rates vary in literature, ranging from 1-8% overall, and limited data exists regarding temporal trends of complication rates. Furthermore, as ablation technology has evolved, it is important to understand how these innovations influence the safety profile. Research Question: To determine the trend of AF catheter ablation complication rates over ten years within a single institution. Methods: All patients undergoing left atrial catheter ablation for AF at Johns Hopkins Hospital from January 1 st , 2015, to December 31 st , 2024, were prospectively enrolled in a comprehensive database. Data including demographics, disease characteristics, procedural data, and 90-day complications were collected via the electronic health record (Epic). Major complications were defined as vascular complications requiring transfusion or surgery, pericardial effusion or tamponade requiring drainage, thromboembolic stroke, sepsis, shock, severe respiratory compromise requiring hospitalization, atrio-esophageal fistula, or death. Results: A total of 2,453 procedures were included. Ablation procedures were grouped into three time periods: 2015-2018 (N=641), 2019-2021 (N=750), and 2022-2024 (N=1062). A total of 87 procedures (3.55%) were associated with complications, including 34 major complications (1.38%) and 53 minor complications (2.16%). Figure 1 shows trends in total, major, and minor complications over time, with a noted significant decrease in major complications (p=0.037). Complication rates were also analyzed by ablation catheter type, as shown in Figure 2. The total complication rate for pulsed field ablation was 2.26% (5/221) compared to an overall complication rate of 3.55%, although this difference was not statistically significant. Conclusion: Major complications from catheter ablation for AF significantly decreased over time within our single-institution cohort. This may be attributed to increasing operator and institutional experience, and incorporation of newer technologies and safety techniques. No statistically significant difference was observed between ablation catheter types. However, this may have been limited by sample size and statistical power, and warrants future investigation.

Introduction and Background: Left lateral atrial ridge (LLR) is sited between the orifices of the left pulmonary veins (PVs) and the left atrial appendage (LAA) ostium and is the crossroads of the vein of Marshall, autonomic nervous system, LAA, PVs and intersected atrial myofibers. Therefore, it may be a substrate for focal triggers initiating AF. Research Questions: We would assess if PVI with bilateral LLR (BLLR) ablation could be superior to PVI alone in long-term maintaining of sinus rhythm in PAF patients without antiarrhythmics drugs (AADs). Methods: In this 1:1 randomized controlled, superiority trial we enrolled 18-80 years old patients undergoing first PAF ablation in our high-volume center. Procedures were performed using pulse field ablation under deep sedation. The primary endpoint is freedom from atrial tachyarrhythmias 12 months after ablation without AADs. The secondary outcome is a composite safety endpoint of all-cause death, cerebrovascular events, cardiac tamponade and all major bleeding. Sample size of 121 patients per group allows to obtain 0,80 statistical power. A structured follow up at 2, 6 and 12 months was settled. Students t-test or non-parametric tests were used to compare continuous variables. Associations between categorical data was evaluated by chi-quare test or Fisher exact test. Log rank test was used to assess the primary outcome. Hazard ratios and confidential intervals were estimated with univariate Cox regression. Results and Data: 34 randomized patients were included in this study preliminary results (mean age 61,4±7,5 years; male 19%). 16 patients were assigned to PVI + BLLR (mean age 62,5±3,9 years; male 11%) and 18 to PVI alone group (mean age 60,4±9,8 years, male 8%). Baseline characteristics of patients are exposed in fig.1. After 6 months, 15 patients (93,7%) assigned to PVI + BLLR were free from recurrent atrial arrhythmia without ADDs, compared with 17 (94,4%) assigned to PVI alone (hazard ratio 0,63; 95% CI 0,03-10,3 p 0,74; Log Rank p 0,66). No secondary outcome events occurred. Procedural time (83±16,5 min versus 82±32,4 min; p 0,4) and first-pass isolation (93,8% versus 100%; p 0,28) were similar between two groups. There was 1 vascular complication per group. Conclusions: Preliminary results of RIDGE AF trial showed no difference in maintaining of sinus rhythm between PVI with BLLR ablation and PVI alone. Further follow up data and enrolled patients are needed to verify this research hypothesis.

Introduction: Transvenous lead extraction (TLE) of old leads is associated with increased procedural complexity and risk due to the development of calcified vascular adhesions. This may necessitate additional tools to free the leads. Shockwave intravenous lithotripsy (IVL), which employs acoustic pressure waves to fracture calcified lesions, has emerged as an adjunctive tool in this setting. However, data on its feasibility in TLE remains limited. Objective: To evaluate the feasibility of IVL as an adjunctive tool in complex TLE cases, focusing on the extraction tools utilized, fluoroscopy duration, success rates, and associated complications. Methods: From a prospectively maintained registry, we analyzed all patients undergoing IVL-assisted TLE at our institution. These patients were matched to controls without IVL using propensity scores derived from baseline and procedural characteristics, including age, sex, infection indication, age of the oldest explanted lead, number of extracted leads, and number of extracted ICDs. A matching ratio of 1:3 was applied to increase statistical power while maintaining covariate balance. Results: A total of 27 patients who underwent lithotripsy were successfully matched to 81 controls. The procedural characteristics are highlighted in Table 1. Mean number of extracted leads and mean age of the oldest extracted lead were comparable between the groups. Patients in the lithotripsy group had significantly higher utilization of laser sheaths alone or combined mechanical and laser sheaths. Median fluoroscopy time was significantly higher in the IVL group (50.2 vs.15.7 mins, p&lt;0.001). Among 27 patients with IVL, complete shockwave applications were performed in 20 patients. In the remaining 7, applications were limited due to stenotic brachiocephalic or superior vena cava veins. Overall, the success and complication rates did not differ significantly between the groups (Fig.1, Table 2). Only one case of vascular laceration with perforation requiring intervention was recorded in the IVL group. The unexpectedly high complication and low success rates in the control group may in part be due to longer dwell times to match the IVL group. Conclusion: We report the largest series on the use of shockwave IVL during complex TLE cases, with significantly higher fluoroscopy times indicating extended procedure durations. Despite favorable safety and efficacy outcomes, the complexity of lead removal remained evident, even with adjunctive IVL.

In genome-wide association studies (GWAS), thousands of genetic variants are tested to identify their associations with a phenotype. GWAS have identified many strongly associated genetic variants with phenotypes and have greatly enhanced our understanding of the genetic architecture of complex phenotypes and diseases. Joint analysis of multiple phenotypes can increase the overall statistical power to detect genetic associations and allows for the identification of pleiotropic loci. A phenotype-phenotype network (PPN) represents phenotypes as nodes and the relationships between them as edges, which allows for the visualization of complex relationships between phenotypes, making it easier to identify clusters and helps us intuitively grasp how different phenotypes are related. In this study, we propose a new method to construct a PPN using the sparse Gaussian Graphical Model (sGGM) based on GWAS summary statistics. This approach isolates the direct relationship between phenotypes, making it easier to identify clusters of phenotypes conditional on other phenotypes that reflect more meaningful biological or functional connections. We then applied a community detection method to partition phenotypes into disjoint modules based on the partial correlation matrix of phenotypes. For each module, various multiple phenotype association tests can be employed to test the association between a SNP and phenotypes in that module. We conducted a comprehensive simulation study to compare the performance of several multiple phenotype association tests using the network modules obtained from sGGM, the correlation matrix, as well as using all phenotypes without modular segmentation. The simulation results demonstrated that most of the multiple phenotype association tests based on network modules from sGGM not only effectively control the Type I error rate but also exhibit higher power compared to network modules derived from the correlation matrix and the association tests on all phenotypes without modular segmentation. We applied this method to the GWAS summary statistics of 92 phenotypes derived from Chapter IX (Diseases of the circulatory system) of ICD-10 codes in the UK Biobank. The results showed that applying multiple phenotype association tests using network modules from the sGGM detected more significant SNPs than using the network modules from the correlation matrix.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22475-4.

Aims: The association between two variables is a fundamental aspect of data analysis across various research fields. Among the many measures of association, Pearson’s, Spearman’s, Kendall’s, Hoeffding’s, Distance Correlation, and Bergsma and Dassios' tau are commonly used in practice. The aim of this study is to compare the statistical power of these six correlation coefficients in detecting various types of relationships, including linear, non-linear, and non-monotonic associations, under different levels of noise and sample sizes. Study Design and Methodology: We evaluate these methods through simulations involving nine specific relationship types (linear, parabolic, cubic, power, sine, exponential, circle, and step function), following the work of Simon and Tibshirani (2011) in their commentary on Reshef et al. (2011). Results: The results demonstrate that Bergsma and Dassios' tau consistently outperforms all other methods for non-linear and non-monotonic relationships, particularly for small sample sizes and complex dependencies. Distance Correlation and Hoeffding’s D also show competitive power, especially for larger sample sizes, but remain generally less powerful than Bergsma and Dassios' tau in small-sample scenarios. For linear relationships, Pearson and Spearman correlations remain the most powerful. Conclusion: These findings highlight the robustness and versatility of Bergsma and Dassios' tau, making it a preferred measure for studies in fields such as social sciences and biology, where small sample sizes and complex relationships are common. Distance Correlation remains a strong alternative for larger datasets, while Pearson and Spearman correlations continue to be effective choices for linear relationships.

Background: Patients with left ventricular assist devices (LVADs) experience high mortality and infection-related complications. While Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits in various populations, their safety and efficacy in advanced heart failure patients on mechanical support remain understudied. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Using ICD-10 and procedural codes, adults with a diagnosis of LVAD (ICD-10: Z95.811) and a history of LVAD-related procedures were identified. Only GLP-1 RAs with proven cardiovascular outcomes -liraglutide, dulaglutide, semaglutide, and tirzepatide- were included. Patients exposed to GLP-1 RAs after LVAD placement formed the GLP1 RA group. Those without GLP-1 RA exposure comprised the control group. Propensity score matching (1:1) was performed on demographics, comorbidities (diabetes, chronic kidney disease, obesity, ischemic heart disease, atrial fibrillation), and medications. Outcomes were assessed over a 5-year follow up period from the index date. The primary outcome was all-cause mortality. Secondary outcomes included hospitalization, device infections, endocarditis, and MRSA/MSSA bloodstream infections. Results: After matching , 543 patients were included in each cohort. The GLP1 group showed significantly lower mortality (17.3% vs. 33.9%, HR 0.40, 95% CI: 0.31–0.51, p&lt;0.001) and higher 5-year survival probability (70.3% vs. 45.6%). Hospitalization was also reduced (69.6% vs. 82.5%, HR 0.44, p&lt;0.001), with longer median time to first admission (241 vs. 34 days). Bloodstream infections were significantly lower in GLP-1 users (20.4% vs. 26.5%, HR 0.61, p=0.001). Device-specific infections was similar in both cohorts (HR 0.86, p=0.13). Endocarditis showed a favorable trend among the GLP-1 RA group but did not reach statistical significance (HR 0.52, p=0.050), possibly due to limited statistical power. Conclusion: In this large real-world analysis, GLP-1 RA use in patients with LVADs was associated with significantly lower long-term mortality, reduced hospitalizations, and fewer bloodstream infections. Although device-specific infections were unaffected, these findings provide observational evidence suggesting possible cardiovascular and infection-related benefits of GLP-1 RAs in advanced heart failure populations. Prospective studies are warranted to confirm safety and efficacy in this unique cohort.

Introduction: Cardiovascular-kidney-metabolic (CKM) syndrome describes the interaction between cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic dysfunction. While acculturation has been associated with increased risk of CVD, less is known about how acculturation associates with CKM syndrome. To date, no studies have examined the relationship between acculturation and CKM syndrome staging. We hypothesize that higher levels of acculturation are associated with more advanced stages of CKM syndrome. Methods: We analyzed data from 4,319 participants of the 2011–2016 National Health and Nutrition Examination Survey (NHANES), a population-based sample of US adults, focusing on adults born outside the US. Based on prior literature, we developed an acculturation score (0-4) based on citizenship (1 point for US citizen), home language (1 point for English spoken ≥50% of the time) and years lived in the US (1 point for ≥5 years, 2 for ≥15 years). We also developed an abridged score using only citizenship and home language (range 0-2) to include more participants. CKM stages were defined as: Stage 0 (no risk factors), Stage 1 (excess adiposity), Stage 2 (metabolic risk or CKD), Stage 3 (predicted 10-year CVD risk ≥20%), and Stage 4 (clinical CVD). Multinominal logistic regression models were used to examine the association between acculturation and CKM stage, adjusting for age, sex, and race. Results: The abridged two-component acculturation score was significantly associated with CKM stage (p=0.02), whereas the three-component score was not (Figures 1a and 1b). Compared to CKM Stage 0, each one-point increment in the abridged score was associated with 27% higher odds of being in CKM Stage 1 (OR 1.27; 95% CI: 1.05–1.53; p &lt; 0.01) and 34% higher odds of being in CKM Stage 4 (OR 1.34; 95% CI: 1.07–1.69; p &lt; 0.01). For the abridged score, mean age was 49.1 years and 51.1% were male (n=2,907). Conclusion: An acculturation score comprising home language and citizenship status was significantly associated with more advanced CKM stages. An acculturation score that also included years lived in the US was not associated with CKM stage, likely due to limited statistical power from missing data. Higher acculturation was associated with both low-risk CKM Stage 1 and clinical CVD in CKM Stage 4. These findings emphasize the need for more comprehensive longitudinal research to better understand the effects of acculturation on CKM progression.

Background: Transcatheter aortic valve replacement (TAVR) is rapidly becoming commonplace for severe symptomatic aortic stenosis (AS). As amyloidosis is becoming more frequently diagnosed, its association with aortic stenosis is coming to light. Cardiac amyloidosis has been historically associated with significant morbidity and mortality. Since many amyloidosis patients may have aortic stenosis, we aimed to assess outcomes in these individuals undergoing TAVR. Hypothesis: Patients with severe aortic stenosis (AS) and concurrent cardiac amyloidosis have worse clinical outcomes compared to those with severe AS alone. Given the increased prevalence of AS among patients with cardiac amyloidosis, would initiating tafamidis therapy prior to transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) improve outcomes in this population? Methods: We utilized the National Inpatient Sample from 2016-2019 to identify 217,575 hospitalized adults who underwent TAVR for AS. These hospitalizations were further stratified based on the presence of Amyloidosis. A multivariate regression model was used to adjust for confounders and analyze the variables. Results: Of those who underwent TAVR, 245 had amyloidosis. In-hospital mortality was higher in those with amyloidosis (3.1% vs 1.4%; p=0.001). Figure 1 shows the Forrest plot for multivariate analysis of periprocedural complications when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, TAVR patients with amyloidosis had longer length of stay (LOS) by 1.2 days (p&lt;0.001) and had additional hospital costs (HC) of $43,160 (p&lt;0.001). Conclusion: TAVR patients who had amyloidosis had significantly worse outcomes in terms of AKI, cardiogenic shock, pneumonia, and atrial fibrillation. There was a trend towards worse outcomes for mortality, LOS, and HC, ventricular tachycardia, vascular complications, intubation, and atrial flutter but was not statistically significant. Some limitations of the study include lack of outpatient follow-up and lower statistical power due to small sample size of amyloidosis patients. Amyloidosis is typically underdiagnosed which could result in their misclassification. While inpatient outcomes seem to be worse in those with amyloidosis. Outpatient follow-up is needed to identify whether this population sees the long-term benefits from TAVR as those without amyloidosis.

Toric intraocular lenses (IOL) predictably correct corneal astigmatism and are an important part of the cataract and refractive surgeon's toolbox. Advances in toric IOL technology, preoperative biometry, IOL power calculations, and IOL alignment have resulted in excellent visual outcomes and achievement of spectacle independence. Despite these advancements, the primary challenges faced in toric IOL use remain choosing the optimal IOL toricity and properly aligning the IOL. Toric IOL are an effective way to correct corneal astigmatism, and advancements in lens selection and design have improved their functionality for patients. This review summarizes these advances and reports on upcoming technologies.