Category: Statistics

Radiother Oncol. 2024 Mar 29:110262. doi: 10.1016/j.radonc.2024.110262. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: To evaluate modern clinical outcomes for patients with brain-only metastatic non-small cell lung cancer (NSCLC) treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site.

MATERIALS AND METHODS: Patients with synchronously diagnosed NSCLC and brain-only metastatic disease treated with intracranial SRS at a single institution were retrospectively identified. Patients were stratified based on whether they did (A) or did not (B) receive definitive primary site treatment. Patient characteristics and clinical outcomes were compared.

RESULTS: From 2008 to 2022, 103 patients were identified, 53 of whom received definitive primary site treatment. Median follow-up was 2.1 y (A) and 0.8 y (B) (p < 0.001). 28 (53 %) patients in Group A received immune checkpoint inhibitor (ICI) therapy versus 19 (38 %) in Group B (p = 0.13) and there were no other statistically significant baseline or treatment characteristic differences between the groups. 5-year local-PFS was 34.5 % (A) versus 0 % (B) (p < 0.001). 5-year regional-PFS was 33.0 % (A) versus 0 % (B) (p < 0.001). 5-year distant body-PFS was 34.0 % (A) versus 0 % (B) (p < 0.001). 5-year CNS-PFS was 14.7 % (A) versus 0 % (B) (p = 0.12). 5-year OS was 40.2 % (A) versus 0 % (B) (p = 0.001). 5-year CSS was 67.6 % (A) versus 0 % (B) (p = 0.002). On multivariable analysis, lack of definitive treatment to the primary site (HR = 2.40), AJCC T3-4 disease (HR = 2.73), and lack of ICI therapy (HR = 2.86) were significant predictors of death.

CONCLUSION: Definitive treatment to the thoracic primary site in patients with brain-only metastatic NSCLC after intracranial radiosurgery was associated with slower progression of disease and improved survival.

PMID:38556172 | DOI:10.1016/j.radonc.2024.110262

J ISAKOS. 2024 Mar 29:S2059-7754(24)00056-7. doi: 10.1016/j.jisako.2024.03.011. Online ahead of print.

ABSTRACT

OBJECTIVES: The goal of this project was to develop and validate a patient-specific, anatomically correct graft for cartilage restoration using magnetic resonance imaging (MRI) data and 3-dimensional (3D) printing technology. The specific aim was to test the accuracy of a novel method for 3D printing and implanting individualized, anatomically shaped bio-scaffolds to treat cartilage defects in a human cadaveric model. We hypothesized that an individualized, anatomic 3D printed scaffold designed from MRI data would provide a more optimal fill for a large cartilage defect compared to a generic flat scaffold.

METHODS: Four focal cartilage defects (FCDs) were created in paired human cadaver knees, age <40 years, in the weight-bearing surfaces of the medial femoral condyle (MFC), lateral femoral condyle (LFC), patella, and trochlea of each knee. MRIs were obtained, anatomic grafts were designed and 3D printed for the left knee as an experimental group, and generic flat grafts for the right knee as a control group. Grafts were implanted into corresponding defects and fixed using tissue adhesive. Repeat post-implant MRIs were obtained. Graft step-off was measured as the distance in mm between the surface of the graft and the native cartilage surface in a direction perpendicular to the subchondral bone. Graft contour was measured as the gap between the undersurface of the graft and the subchondral bone in a direction perpendicular to the joint surface.

RESULTS: Graft step-off was statistically significantly better for the anatomic grafts compared to the generic grafts in the MFC (0.0±0.2 mm vs. 0.7±0.5 mm, p<0.001), LFC (0.1±0.3 mm vs. 1.0±0.2 mm, p<0.001), patella (-0.2±0.3 mm vs. -1.2±0.4 mm, p<0.001), and trochlea (-0.4±0.3 vs. 0.4±0.7, p=0.003). Graft contour was statistically significantly better for the anatomic grafts in the LFC (0.0±0.0 mm vs. 0.2±0.4 mm, p=0.022) and trochlea (0.0±0.0 mm vs. 1.4±0.7 mm, p<0.001). The anatomic grafts had an observed maximum step-off of -0.9 mm and a maximum contour mismatch of 0.8 mm.

CONCLUSION: This study validates a process designed to fabricate anatomically accurate cartilage grafts using MRI and 3D printing technology. Anatomic grafts demonstrated superior fit compared to generic flat grafts.

LEVEL OF EVIDENCE: Level IV.

PMID:38556170 | DOI:10.1016/j.jisako.2024.03.011

J Stomatol Oral Maxillofac Surg. 2024 Mar 29:101854. doi: 10.1016/j.jormas.2024.101854. Online ahead of print.

ABSTRACT

INTRODUCTION: The present study aimed to identify the morphological differences in cranial and dentofacial structures between individuals with mouth-breathing and nasal-breathing.

MATERIALS AND METHODS: The study included 120 individuals, 60 each in the nasal breathing (NB) and mouth breathing (MB) groups. 3D stereophotogrammetry, lateral cephalometric radiographs, and intraoral examination results were recorded by the researchers to determine the morphological differences between the MB group and the NB group. The study utilized cephalometric radiographs for 2D hard tissue measurements and 3D stereophotogrammetric records for linear and angular measurements.

RESULTS: Statistically significant differences were found between the NB and MB groups’ SNB angles (respectively, 79.3±3.04, 76.6±4.24, and p=0.002). Also, the NB group’s SN-GoGn angle was lower than the MB group’s (respectively, 31.5±5.12, 36.0±5.55, and p=0.002). Considering the Jarabak ratio, the NB group’s Jarabak ratio was higher than the MB group (respectively,65.7±4.16, 62.6±4.10, and p=0.014). In 3D stereophotogrammetry measurements, increased Li-Me’ was detected in the MB group than in NB group.

CONCLUSION: Mouth breathing results in significant morphological differences that affect the development of both soft tissues and skeletal structures. Orthodontists utilize these characteristic features observed in mouth-breathing anomalies for early diagnosis and consider referring their patients for medical treatment of mouth breathing.

PMID:38556168 | DOI:10.1016/j.jormas.2024.101854

J Stomatol Oral Maxillofac Surg. 2024 Mar 29:101857. doi: 10.1016/j.jormas.2024.101857. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to quantify the facial symmetry of surgically treated zygomaticomaxillary complex (ZMC) fractures through a new reliable three-dimensional evaluation method, which is crucial for improving post-operative aesthetic and functional outcomes.

MATERIAL AND METHODS: Healthy patients and patients with surgically treated ZMC fractures were retrospectively reviewed. Using Brainlab Elements® the zygomatic bone and the orbit of each patient was segmented and mirrored. Subsequently, the mirrored side was matched with the other side via volume-based registration, using the segmented orbit as reference. Volumetric asymmetry was measured using 3-matic software, and a surface-based matching technique was used to calculate the mean absolute differences (MAD) between the surfaces of the two sides of the ZMC. The reliability of this novel method using volume-based registration was tested, and the intra-class correlation coefficient was assessed.

RESULTS: The MAD between the surfaces of the left and right sides in the control group was 0.51 mm (±0.09). As for the ZMC fracture group, MAD was 0.78 mm (±0.20) and 0.72 mm (±.15) pre- and post-operatively, respectively. The MAD showed statistically significant differences between pre- and post-operative groups (p = 0.005) and between control and post-operative groups (p < 0.001). The intra-class correlation coefficient was high (≥ 0.99).

CONCLUSIONS: This evaluation method using mirroring and volume-based registration to determine the symmetrical position of the ZMC is reliable. The surface-based measurements revealed an improved symmetry after surgery. However, the symmetry of the treated patients remained lower than the control group.

PMID:38556166 | DOI:10.1016/j.jormas.2024.101857

J Stomatol Oral Maxillofac Surg. 2024 Mar 29:101858. doi: 10.1016/j.jormas.2024.101858. Online ahead of print.

ABSTRACT

INTRODUCTION: Head and neck cancer squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with around 600000 new diagnosis each year. Nowadays, in locally advanced disease, radiotherapy (RT) play an important role, this with or without chemotherapy in organ preservation strategies. More specific for early stage localized disease, RT (or surgery) seems to give similar results on locoregional control (LRC) and choice is made according to the organ preservation issue. Despite the fact that technical improvements have been made to optimize the radiation dose delivery and minimize the normal tissue toxicity, RT is associated with potential early and late toxicities. Osteoradionecrosis of the jaw (ORNJ), especially seen after teeth extraction, is one of the associated toxicities and can significantly impair the patient’s quality of life. Because of the fear of developing ORNJ, one is very reluctant to extract or place a dental implant post-radiotherapy, especially in high irradiation dose zones (>40Gy). Hence, it is important to define teeth at risk of future extraction before initiating RT and to handle those in high-risk irradiation zones. In order to optimise extractions, we created a predictive model of the expected irradiation dose, and thus the need for extraction, to the teeth bearing bones. The aim of this study is to validate our model and to define the potential relationship between the radiation dose received by each tooth and the dental complications observed.

MATERIAL AND METHODS: Between March 2012 and March 2018, patients with HNSCC treated by intensity modulated RT were retrospectively analyzed. The mean irradiation dose for each tooth was generated on the administered treatment plan by contouring each tooth separately on each dosimetric scan section using dedicated software (Eclipse, Varian). In order to validate our predictive model, we compared the actual generated/administered teeth irradiation doses with the irradiation doses predicted by our model.

RESULTS: Our predictive model was accurate in 69.6% of the cases. In 12.5% of cases the predicted dose was higher than the calculated dose and lower in 17,8 % of the cases. A correct- or over-estimation (is the latter being clinically less worrying than an underestimated dose) was achieved in 82% of cases. For the 18% of cases underfitting, the mean margin of error was 5.7Gy. No statistically significant association was found between the development of caries and doses to the teeth, doses to the parotid glands or dental hygiene. However, a significant association between dental irradiation at more than 40Gy and the occurrence of dental fractures (p=0.0002) were demonstrated.

CONCLUSIONS: Our predictive model seems to be 82 % accurate for dose prediction, hence might be helpful for optimizing/minimizing prophylactic extractions. Indeed, following our model, professionals could decide not to extract damaged teeth in areas not at risk of ORNJ, lowering morbidity during and after RT. Contrary to the literature, no relationship was found between the occurrence of dental caries and parotid irradiation and the patient’s oral hygiene. However, for the first time, a highly significant correlation between the occurrence of dental fracture and dental irradiation at more than 40Gy was observed.

PMID:38556165 | DOI:10.1016/j.jormas.2024.101858

J Stomatol Oral Maxillofac Surg. 2024 Mar 29:101844. doi: 10.1016/j.jormas.2024.101844. Online ahead of print.

ABSTRACT

A novel approach to Le Fort I osteotomy is presented, integrating patient-specific implants (PSIs), osteosynthesis and cutting guides within a minimally invasive surgical framework, and the accuracy of the procedure is assessed through 3D voxel-based superimposition. The technique was applied in 5 cases. Differences between the surgical plan and final outcome were evaluated as follows: a 2-mm color scale was established to assess the anterior surfaces of the maxilla, mandible and chin, as well as the condylar surfaces. Measurements were made at 8 specific landmarks, and all of them showed a mean difference of less than 1 mm. In conclusion, the described protocol allows for minimally invasive Le Fort I osteotomy using PSIs. Besides, although the accuracy of the results may be limited by the small sample size, the findings are consistent with those reported in the literature. A prospective comparative study is needed to obtain statistically significant results and draw meaningful conclusions.

PMID:38556164 | DOI:10.1016/j.jormas.2024.101844

J Mol Diagn. 2024 Mar 27:S1525-1578(24)00062-X. doi: 10.1016/j.jmoldx.2024.03.004. Online ahead of print.

ABSTRACT

Applied Artificial Intelligence, particularly Large Language Models, in biomedical research is accelerating, but effective discovery and validation requires a toolset without limitations or bias. On January 30, 2023, the National Academies of Sciences, Engineering, and Medicine (NAS) appointed an ad hoc committee to identify needs and opportunities to advance the mathematical, statistical, and computational foundations of digital twins in applications across science, medicine, engineering, and society. On December 15, 2023, the NAS released a 164 page report, “Foundational Research Gaps and Future Directions for Digital Twins”. This report described the importance of using digital twins in biomedical research. We developed an innovative method that incorporated phenotype ranking algorithms with knowledge engineering via a biomimetic digital twin ecosystem. This ecosystem applied real-world reasoning principles to non-normalized, raw data to identify hidden or “dark data”. We performed a clinical exome sequencing study on patients with endometriosis and were able to identify four VUSs potentially associated with endometriosis-related disorders in nearly all patients analyzed. One VUS was identified in all patient samples and could be a biomarker for diagnostics. To the best of our knowledge, this is the first study to incorporate the recomandations of the NAS to biomedical research. This method can be used to understand the mechanisms of any disease, for virtual clinical trials, and to identify effective new therapies.

PMID:38556123 | DOI:10.1016/j.jmoldx.2024.03.004

Reprod Toxicol. 2024 Mar 29:108582. doi: 10.1016/j.reprotox.2024.108582. Online ahead of print.

ABSTRACT

The objective of this meta-analysis is to investigate the association between air pollution and the vulnerability of children to autism spectrum disorders (ASD). A thorough examination and analysis of data obtained from a compilation of 14 studies was undertaken, with a particular emphasis on investigating the effects of nitrogen dioxide (NO₂), oxide of nitrogen (NO_x), ozone (O₃), and particulate matter (PM₁₀ and PM_2.5) on individuals diagnosed with ASD. The findings demonstrate a moderate association between exposure to nitrogen dioxide (NO₂) and ASD, as indicated by a combined odds ratio (OR) of 1.13 and a 95% confidence interval (CI) spanning from 0.77 to 1.549. O₃ shows a combined odds ratio (OR) of 0.82, along with a 95% confidence interval (CI) ranging from 0.49 to 1.14. NO_x shows a moderate level of heterogeneity (I² = 75.9%, p = 0.002), suggesting that the impact of NO_x on the risk of ASD. There is a statistically significant relationship between exposure to O₃ and ASD, although the strength of this relationship is diminished. The findings demonstrated a noteworthy correlation between exposure to PM₁₀ and PM_2.5 and the occurrence of ASD. The study found a significant correlation, in relation to PM_2.5, with a combined odds ratio (OR) of 1.22 and a 95% confidence interval (CI) ranging from 1.11 to 1.34. The findings have significant implications for the formulation of programs aimed at reducing exposure to harmful chemicals, especially among vulnerable groups such as children.

PMID:38556115 | DOI:10.1016/j.reprotox.2024.108582

J Acad Nutr Diet. 2024 Mar 29:S2212-2672(24)00145-X. doi: 10.1016/j.jand.2024.03.012. Online ahead of print.

ABSTRACT

INTRODUCTION: The relationship between the retail food environment and diet quality has received minimal investigation among weight loss maintainers.

OBJECTIVE: To investigate the association between the residential retail food environment and diet quality in weight loss maintainers from WeightWatchers (WW) in the US.

DESIGN: Cross-sectional data were collected between January 2018 and February 2020. The Retail Food Environment Index (RFEI), based on geocoded home addresses, classified the environment: RFEI < 1.6= healthiest; RFEI 1.6- <2.5, = moderately healthy; RFEI 2.5 – <4.0 = moderately unhealthy; RFEI ≥4.0= least healthy. Dietary data was obtained using a food frequency questionnaire.

PARTICIPANTS: /setting: Adult participants (n=1,159) who had lost weight using WW and maintained >9.1 kg weight loss for > 1 year (mean 24.7 kg loss for 3.4 years).

OUTCOME MEASURES: HEI-2015 component and total scores (0-100; higher scores indicate better alignment with the Dietary Guidelines for Americans 2015-2020).

STATISTICAL METHODS: Regression models included RFEI category, the independent variable, and HEI-2015 and component scores (outcomes) controlling for age, sex, race and ethnicity, educational attainment, and household income.

RESULTS: Compared to individuals living in the healthiest food environments (mean HEI-2015 score = 71.5) those in the unhealthiest environments had a mean HEI-2015 score of 70.1 (95% CI = 68.8, 71.3), those in moderately unhealthy environments had a score of 71.3 (95% CI = 70.3, 73.1) and those in moderately healthy environments had a score of 70.3 (95% CI=68.9, 71.2), indicating a non-linear relationship. Compared to those in the healthiest environments, those in the least healthy had approximately a 0.47 lower added sugar HEI-2015 component score (95% CI = -0.86, -0.08), indicating approximately 5% higher added sugar intake.

CONCLUSIONS: Weight loss maintainers maintained high diet quality in diverse retail food environments. Compared to those in healthiest food environments, those in the least healthy had a higher consumption of added sugars.

PMID:38556111 | DOI:10.1016/j.jand.2024.03.012

J Clin Epidemiol. 2024 Mar 29:111338. doi: 10.1016/j.jclinepi.2024.111338. Online ahead of print.

ABSTRACT

Causal inference methods for observational data represent an alternative to randomised controlled trials when they are not feasible or when real-world evidence is sought. Inverse-probability-of-treatment weighting (IPTW) is one of the most popular approaches to account for confounding in observational studies. In medical research, IPTW is mainly applied to estimate the causal effect of a binary treatment, even when the treatment has in fact multiple categories, despite the availability of IPTW estimators for multiple treatment categories. This raises questions about the appropriateness of the use of IPTW in this context. Therefore, we conducted a systematic review of medical publications reporting the use of IPTW in the presence of a multi-category treatment. Our objectives were to investigate the frequency of use and the implementation of these methods in practice, and to assess the quality of their reporting. This systematic review is registered on PROSPERO (CRD42022352669). Using Pubmed, Embase and Web of Science, we screened 5660 articles and retained 106 articles in the final analysis that were from 17 different medical areas. The number of treatment groups varied between 3 and 9, with a large majority of articles (90 (84.9%)) including 3 or 4 groups. The most commonly used method for estimating the weights was multinomial regression (51 (48.1%)) and generalized boosted models (48 (45.3%)). The covariates of the weight model were reported in 91 articles (85.9 %). Twenty-six articles (24.5 %) did not discuss the balance of covariates after weighting, and only 16 articles (15.1 %) referred to the assumptions needed to obtain correct inferences. The results of this systematic review illustrate that medical publications scarcely use IPTW methods for more than two treatment categories. Among the publications that did, the quality of reporting was suboptimal, in particular in regard to the assumptions and model building. IPTW for multi-category treatments could be applied more broadly in medical research, and the application of the proposed guidelines in this context will help researchers to report their results and to ensure reproducibility of their research.

PMID:38556101 | DOI:10.1016/j.jclinepi.2024.111338