Category: Statistics

Transl Psychiatry. 2024 Nov 23;14(1):476. doi: 10.1038/s41398-024-03184-4.

ABSTRACT

Autism spectrum disorder (ASD) often co-occurs with functional somatic syndromes (FSS), such as irritable bowel syndrome (IBS), multisite pain, and fatigue. However, the underlying genetic mechanisms and causality have not been well studied. Using large-scale genome-wide association study (GWAS) data, we investigated the shared genetic architecture and causality between ASD and FSS. Specifically, we first estimated genetic correlations and then conducted a multi-trait analysis of GWAS (MTAG) to detect potential novel genetic variants for single traits. Afterwards, polygenic risk scores (PRS) of ASD were derived from GWAS and MTAG to examine the associations with phenotypes in the large Dutch Lifelines cohort. Finally, we performed Mendelian randomization (MR) to evaluate the causality. We observed positive genetic correlations between ASD and FSS (IBS: r_g = 0.27, adjusted p = 2.04 × 10^-7; multisite pain: r_g = 0.13, adjusted p = 1.10 × 10^-3; fatigue: r_g = 0.33, adjusted p = 5.21 × 10^-9). Leveraging these genetic correlations, we identified 3 novel genome-wide significant independent loci for ASD by conducting MTAG, mapped to NEDD4L, MFHAS1, and RP11-10A14.4. PRS of ASD derived from both GWAS and MTAG were associated with ASD and FSS in Lifelines, and MTAG-derived PRS showed a bigger effect size, larger explained variance, and smaller p-values. We did not observe significant causality using MR. Our study found genetic associations between ASD and FSS, specifically with IBS, multisite pain, and fatigue. These findings suggest that a shared genetic architecture may partly explain the co-occurrence between ASD and FSS. Further research is needed to investigate the causality between ASD and FSS due to current limited statistical power of the GWASs.

PMID:39580447 | DOI:10.1038/s41398-024-03184-4

Int J Equity Health. 2024 Nov 23;23(1):247. doi: 10.1186/s12939-024-02333-x.

ABSTRACT

BACKGROUND: Enhancing the accessibility and equity of primary healthcare (PHC) is a crucial objective of China’s healthcare reform. However, spatial barriers remain a significant factor contributing to the inequitable access to PHC services among residents.

OBJECTIVE: This study aims to quantify the spatial accessibility (SA) and evaluate the equity of PHC resources in a pilot province for healthcare reform, and its municipalities, thereby providing insights that can be generalized to the broader context of China.

METHODS: The study used the navigation function provided by Gaode Map to estimate the time it takes for residents to visit PHC institutions. The two-step floating catchment area (2SFCA) method, weighted by a Gaussian function, was employed to measure the SA of PHC institutions, general practitioners (GPs), and beds across various residential areas. The Gini coefficient was utilized to assess disparities in SA among different regions. Additionally, Getis-Ord Gi* analysis was conducted to visualize these spatial disparities.

RESULTS: The study analyzed 25,601 residential and 1,451 healthcare points in Zhejiang Province, revealing significant disparities in SA of PHC. Urban residents reached PHC institutions faster than rural ones (7.05 ± 4.7 min vs. 9.17 ± 7.78 min, P < 0.001). Within 30 min, 98.4% of residential points and 99.1% of the population accessed PHC institutions. Disparities in PHC resources were notable, with Lishui having the highest SA for institutions and GPs, and Shaoxing for beds. Equity assessment showed high inequity for institutions (Gini 0.553), moderate for beds (Gini 0.497), and reasonable for GPs (Gini 0.332)​. Getis-Ord Gi* analysis demonstrated that areas further from urban centers were more likely to exhibit clusters of hotspots or cold spots.

CONCLUSION: The study highlights substantial disparities in SA of PHC and equity across Zhejiang, underscoring the need for strategic resource distribution. Future research should include diverse transportation modes and more precise demand point data to enhance understanding of accessibility dynamics.

PMID:39580443 | DOI:10.1186/s12939-024-02333-x

BMC Med Res Methodol. 2024 Nov 23;24(1):290. doi: 10.1186/s12874-024-02408-x.

ABSTRACT

BACKGROUND: Patient-reported outcomes (PROs) play an increasing role in the evaluation of oncology treatments. At the same time, single-arm trials are commonly included in regulatory approval submissions. Because of the high risk of biases, results from single-arm trials require careful interpretation. This benefits from a clearly defined estimand, or target of estimation. In this case study, we demonstrated how the ICH E9 (R1) estimand framework can be implemented in SATs with PRO endpoints.

METHODS: For the global quality of life outcome in a real single-arm lung cancer trial, a range of possible estimands was defined. We focused on the choice of the variable of interest and strategies to deal with intercurrent events (death, treatment discontinuation and disease progression). Statistical methods were described for each estimand and the corresponding results on the trial data were shown.

RESULTS: Each intercurrent event handling strategy resulted in its own estimated mean global quality of life over time, with a specific interpretation, suitable for a corresponding clinical research aim. In the setting of this case study, a ‘while alive’ strategy for death and a ‘treatment policy’ strategy for non-terminal intercurrent events were deemed aligned with a descriptive research aim to inform clinicians and patients about expected quality of life after the start of treatment.

CONCLUSIONS: The results show that decisions made in the estimand framework are not trivial. Trial results and their interpretation strongly depend on the chosen estimand. The estimand framework provides a structure to match a research question with a clear target of estimation, supporting specific clinical decisions. Adherence to this framework can help improve the quality of data collection, analysis and reporting of PROs in SATs, impacting decision making in clinical practice.

PMID:39580440 | DOI:10.1186/s12874-024-02408-x

Fam Process. 2024 Nov 23. doi: 10.1111/famp.13084. Online ahead of print.

ABSTRACT

The rising rates of adolescent depression have become a critical concern, with family dynamics and interpersonal communication playing a significant role in this mental health issue. However, research on the combined effects of parental warmth and interpersonal trust on adolescent depressive symptoms remains limited. This study aimed to explore the association between parental warmth, interpersonal trust, and depressive symptoms in Chinese adolescents. The sample included 2745 adolescents aged 9 to 18 from the China Family Panel Studies (CFPS). Depressive symptoms were assessed using the CES-D8 scale, which yielded an average score of 4.34. Among participants, 11.3% exhibited symptoms consistent with depression. Multivariate linear regression revealed that both parental warmth (β = -0.296, p < 0.001) and interpersonal trust (β = -0.197, p < 0.001) significantly predicted lower depressive symptoms. Mediation analysis indicated that interpersonal trust partially mediated the relationship between parental warmth and depressive symptoms, explaining 17.68% of the total effect (β = -0.032, 95% CI = -0.060, -0.016). These associations remained significant even after controlling for demographic variables. Our findings suggest that parental warmth protects against depressive symptoms, with interpersonal trust enhancing this protective effect. Interventions focused on fostering parental warmth and enhancing interpersonal trust could improve adolescent mental health.

PMID:39579012 | DOI:10.1111/famp.13084

Orthop Surg. 2024 Nov 23. doi: 10.1111/os.14304. Online ahead of print.

ABSTRACT

OBJECTIVE: Currently, there is no research that includes a comprehensive three-dimensional fracture mapping encompassing all types of Pilon fractures. Moreover, the existing classification systems for Pilon fractures exhibit only moderate to fair consistency and reproducibility. Additionally, some of these classification systems fail to accurately depict the morphological characteristics of the fractures. This study aimed to create a fracture map encompassing all types of Pilon fractures by three-dimensional fracture mapping. In addition, this study conducted a finite element analysis of the normal ankle joint, and based on the distribution of fracture lines and the stress distribution at the distal tibia, proposed a new classification for Pilon fractures.

METHODS: A retrospective analysis of Pilon fractures in our hospital from January 2018 to January 2024 was performed. A total of two hundred forty-four Pilon fractures were included, and their fracture lines were transcribed onto the tibia and fibula templates, and fracture maps and heat maps were created. A nonhomogeneous model of the ankle joint was constructed and verified, and the stress distribution on the distal tibia articular surface was measured and analyzed in three models (neutral, dorsiflexed, and plantarflexed model). Based on the fracture map and stress distribution, a five-column classification system for Pilon fractures was proposed, and the intraobserver and interobserver reliability was calculated using Cohen and Fleiss k statistics.

RESULT: The fracture line on the distal tibia articular surface showed a V-shaped distribution. One branch extended from the junction of the medial malleolar articular surface and the inferior tibial articular surface toward the medial malleolus. The other branch extended from the middle of the fibular notch to the posterior part of the medial ankle, toward the tibial shaft. The fibula fracture line mainly extended from the anterior and lower part of the lateral malleolus to the posterior and upper part. As evidenced by the neutral, dorsiflexed, and plantar flexion models, the stress on the posterolateral articular surface (posterolateral column) was low, while the majority of the stress was concentrated in the center. Three-column fractures were the most common, followed by two-column fractures. Using the five-column classification, the K-weighted values of interobserver and intraobserver analysis were 0.653 (p < 0.001) and 0.708 (p < 0.001), respectively.

CONCLUSIONS: In this study, the fracture line and morphological characteristics of Pilon fractures were analyzed in detail by three-dimensional mapping. In addition, this study conducted a finite element analysis of the stress distribution on the distal tibial joint surface of the normal ankle joint. Moreover, a novel classification system was proposed to reflect these findings. The new classification not only exhibits greater consistency, facilitating accurate communication of fracture characteristics among surgeons, but also aids in understanding the mechanisms of injury and formulating surgical strategies.

PMID:39579007 | DOI:10.1111/os.14304

Ophthalmic Physiol Opt. 2024 Nov 23. doi: 10.1111/opo.13393. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Associations between the occurrence of early age related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported, based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, we designed an omics-type approach for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole.

METHODS: A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For each participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At every position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for each descriptor at every graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure.

RESULTS: In terms of the amount and disparity of true discoveries, overall non-equivalence was found for early AMD and healthy groups. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise.

CONCLUSIONS: Between the retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoon and speckle bear essential parts of the total information. We pursued a constructive, completely documented, traceable and repeatable approach without invoking artificial intelligence methods.

PMID:39579005 | DOI:10.1111/opo.13393

Ophthalmic Physiol Opt. 2024 Nov 23. doi: 10.1111/opo.13392. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Associations between the occurrence of early age-related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, an omics-type approach was designed for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole.

METHODS: A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For every participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At each position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for every descriptor at each graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure.

RESULTS: In terms of the amount and disparity of true discoveries, overall non-equivalence of early AMD and healthy groups was found. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise.

CONCLUSIONS: Between retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within the OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but also the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoons and speckle bear essential parts of total information. A constructive, completely documented, traceable and repeatable approach was pursued without invoking artificial intelligence methods.

PMID:39579003 | DOI:10.1111/opo.13392

Biometrics. 2024 Oct 3;80(4):ujae138. doi: 10.1093/biomtc/ujae138.

ABSTRACT

With the advent of massive survival data with a cure fraction, large-scale regression for analyzing the effects of risk factors on a general population has become an emerging challenge. This article proposes a new probability-weighted method for estimation and inference for semiparametric cure regression models. We develop a flexible formulation of the mixture cure model consisting of the model-free incidence and the latency assumed by the semiparametric proportional hazards model. The susceptible probability assesses the concordance between the observations and the latency. With the susceptible probability as weight, we propose a weighted estimating equation method in a small-scale setting. Robust nonparametric estimation of the weight permits stable implementation of the estimation of regression parameters. A recursive probability-weighted estimation method based on data blocks with smaller sizes is further proposed, which achieves computational and memory efficiency in a large-scale or online setting. Asymptotic properties of the proposed estimators are established. We conduct simulation studies and a real data application to demonstrate the empirical performance of the proposed method.

PMID:39578979 | DOI:10.1093/biomtc/ujae138

Biometrics. 2024 Oct 3;80(4):ujae134. doi: 10.1093/biomtc/ujae134.

ABSTRACT

The development of sensors is opening new avenues in several fields of activity. Concerning agricultural crops, complex combinations of agri-environmental dynamics, such as soil and climate variables, are now commonly recorded. These new kinds of measurements are an opportunity to improve knowledge of the drivers of crop yield and crop quality at harvest. This involves renewing statistical approaches to account for the combined variations of these dynamic variables, here considered as temporal variables. The objective of the paper is to estimate an interpretable model to study the influence of the two combined inputs on a scalar output. A Sparse and Structured Procedure is proposed to Identify Combined Effects of Formatted temporal Predictors, hereafter denoted S piceFP. The method is based on the transformation of both temporal variables into categorical variables by defining joint modalities, from which a collection of multiple regression models is then derived. The regressors are the frequencies associated with joint class intervals. The class intervals and related regression coefficients are determined using a generalized fused lasso. S piceFP is a generic and exploratory approach. The simulations we performed show that it is flexible enough to select the non-null or influential modalities of values. A motivating example for grape quality is presented.

PMID:39578978 | DOI:10.1093/biomtc/ujae134

J Endovasc Ther. 2024 Nov 23:15266028241292954. doi: 10.1177/15266028241292954. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal endovascular method to treat infrapopliteal chronic limb-threatening ischemia (CLTI) remains to be determined, given the limitations of stent use in infrapopliteal artery disease. We performed a network meta-analysis (NWM) of randomized controlled trials (RCTs) to simultaneously compare the outcomes of different balloon angioplasty procedures for infrapopliteal artery lesions in CLTI patients.

METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, and PubMed. 8 eligible RCTs involving 3 endovascular modalities or combinations (plain old balloon angioplasty [POBA], drug-coated balloon [DCB], orbital atherectomy plus plain old balloon angioplasty [OA+POBA]) were included. Primary outcomes were efficacy (12-month clinically driven target lesion revascularization [CDTLR]) and safety (12-month major amputation and all-cause mortality). We used random-effects models based on the frequentist framework.

RESULTS: Plain old balloon angioplasty had a higher 12-month CDTLR rate than DCB (relative risk [RR]: 2.11, confidence interval [CI]: 1.33, 3.34) in the NWM and this result was still statistically significant (RR: 0.47, CI: 0.30, 0.75) in subgroup analyses. According to the SUCRA value, in terms of 12-month CDTLR, OA+POBA was considered the best treatment (SUCRA=72.2), while POBA was considered the worst treatment (SUCRA=8.9). In terms of 12-month all-cause mortality, OA+POBA was considered the best treatment (SUCRA=95.0), while DCB was considered the worst treatment (SUCRA=12.8). In terms of 12-month major amputation, POBA was considered the best treatment (SUCRA=72.0), while DCB was considered the worst treatment (SUCRA=23.0).

CONCLUSIONS: In infrapopliteal CLTI disease, DCB showed a significantly lower 12-month CDTLR in comparison to POBA. There is no statistically significant evidence to suggest that DCB raises safety concerns. The SUCRA values of OA+POBA indicate that it might offer a superior treatment option compared to DCB or POBA in terms of CDTLR and mortality. This advantage, however, was not sustained when major-amputation rates were analyzed. Consequently, further RCTs are required to examine the potential benefits of OA and other forms of atherectomy for managing infrapopliteal CLTI disease.

CLINICAL IMPACT: The findings of this study provide further evidence for the safety of DCB in the application of infrapopliteal CLTI disease and suggest preliminary benefits of atherectomy. These results are likely to encourage further research and application of these treatment modalities in managing infrapopliteal CLTI.POBA has been a traditional approach for treating infrapopliteal artery disease. The current evidence supports clinicians in exploring and utilizing DCB and atherectomy as better treatments.We focused on the performance of different balloon angioplasty procedures in infrapopliteal CLTI, considering the characteristics of infrapopliteal CLTI.

PMID:39578965 | DOI:10.1177/15266028241292954