Landmark Approach Research Articles

Towards Data-and Knowledge-Driven AI: A Survey on Neuro-Symbolic Computing.

Neural-symbolic computing (NeSy), which pursues the integration of the symbolic and statistical paradigms of cognition, has been an active research area of Artificial Intelligence (AI) for many years. As NeSy shows promise of reconciling the advantages of reasoning and interpretability of symbolic representation and robust learning in neural networks, it may serve as a catalyst for the next generation of AI. In the present paper, we provide a systematic overview of the recent developments and important contributions of NeSy research. Firstly, we introduce study history of this area, covering early work and foundations. We further discuss background concepts and identify key driving factors behind the development of NeSy. Afterward, we categorize recent landmark approaches along several main characteristics that underline this research paradigm, including neural-symbolic integration, knowledge representation, knowledge embedding, and functionality. Next, we briefly discuss the successful application of modern NeSy approaches in several domains. Then, we benchmark several NeSy methods on three representative application tasks. Finally, we identify the open problems together with potential future research directions. This survey is expected to help new researchers enter this rapidly evolving field and accelerate the progress towards data-and knowledge-driven AI.

Stature estimation equations from fragmentary long bones based on a modern Eastern Mediterranean assemblage.

Stature estimation is central in forensic anthropology and very important in bioarchaeology. For this reason, several different methods have been proposed, employing different skeletal elements and statistical approaches. A major issue with skeletonized individuals is that their bones are often found fragmented, a taphonomic parameter that limits the application of many available methods. As a result, attempts have been made to create equations to predict either directly stature or long bone length (which can then be used with current stature prediction equations) from bone fragments. The current paper is a contribution in this direction. The femur, tibia and humerus of 76 individuals from a modern Greek skeletal collection were divided into different segments using a landmark approach. Subsequently, univariate and multivariate equations were created to predict both maximum long bone length and stature from the "bone fragments". The models varied in performance depending on the specific bone fragment used, the number of variables simultaneously employed for prediction and the sex of the individuals. Although the models used to directly predict stature from bone fragment dimensions should be treated cautiously because the stature of the assemblage from the Athens Collection had itself been anatomically estimated, the results are valuable towards highlighting the complex association between bone dimensions, long bone length and living/estimated stature.

Ultrasound-Guided Suprainguinal Fascia Iliaca Compartment Block in Patients Undergoing Hip Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The use of fascia iliaca compartment block (FICB) has been widely encouraged for hip surgery; however, meta-analyses showed mixed results in terms of its efficacy in reduction in analgesic consumption and pain score. These meta-analyses included all forms of FICB approaches, which may diminish the effect size of the therapy. Suprainguinal FICB (s-FICB) has been shown to be superior to other FICB approaches including the ultrasound-guided infrainguinal approach and the landmark approach. This systematic review and meta-analysis aim to compare opioid consumption, pain score, and complications after s-FICB to control for patients undergoing hip surgery. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42023460377). We performed a systematic literature search in Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases from inception to 16August 2023 to identify randomized controlled trials (RCTs) that evaluated the efficacy of s-FICB versus control for patients undergoing hip surgery. Data were independently extracted by two reviewers, and disagreements were resolved by consensus or by discussion with a third investigator. The primary outcome is the 24-houroral morphine equivalent daily dose (oMMED). The secondary outcome includes oMMED at different timepoints, and pain score. The Cochrane risk of biastool (Cochrane, London, England) was used to assess the risk of bias. The certainty of evidence was assessed via the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data were synthesized using a random-effects model. Trial sequence analysis is performed on opioid consumption 24 hours post operation. Eleven randomized controlled trials were included. Arthroscopic hip surgery was performed in three studies involving 222 patients, hip and femur fracture surgeries were performed in three studies involving 149 patients, and total hip arthroplasty was performed in five studies involving 483 patients. In studies involving arthroscopic hip surgery, s-FICB did not improve intra-operative and post-operative opioid consumption and post-operative pain score. In studies involving hip and femur fracture surgeries, s-FICB was associated with a non-significant difference in opioid consumption at 24 hours after surgery and post-operative pain score at 12 hours and 24 hours after surgery. However, the result of the trial sequential analysis (TSA) was not definitive, indicating that additional research is necessary to draw conclusive outcomes. In studies involving total hip arthroplasty, s-FICB was associated with a significant reduction in post-operative opioid consumption at 24 and 48 hours with conclusive results in trial sequential analysis. In conclusion, s-FICB is superior to placebo for patients undergoing total hip arthroplasty. For patients undergoing arthroscopic hip surgery, s-FICB is unlikely to be beneficial. With regardto hip fracture surgery, additional research is necessary to draw conclusive outcomes.

Phosphodiesterase 5 Inhibitor Treatment Is Associated With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry

BackgroundPatients with COPD frequently develop pulmonary hypertension (PH-COPD). Severe PH-COPD, identified by a pulmonary vascular resistance (PVR) >5 Wood Units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear. Research QuestionIs PH-targeted therapy associated with improved transplant-free survival in PH-COPD? Study Design and MethodsThis study included PVRI GoDeep meta-registry patients with PH-COPD and available right heart catheterization at diagnosis. We investigated PH-targeted therapy prevalence and its association with transplant-free survival using diverse statistical methods, including Cox regression and subgroup analyses based on PH severity, comorbidities, and pulmonary function tests. Immortal time bias was addressed through a landmark approach. ResultsAs of December 2023, the GoDeep meta-registry included 26981 patients (28% PH-Group 1, 13% PH-Group 2, 12% PH-Group 3, 10% PH-Group 4, 2% PH-Group 5, 26% undefined and 9% control). Out of these, 836 patients were diagnosed as PH-COPD and included in this analysis, with median age 66 [59,73]years, FEV1 51 [34,69]%predicted, mPAP 35 [28,44]mmHg, PVR 5 [4,8]WU, cardiac index 2.5 [2.0,2.9]L/min.m2, and mostly WHO functional class III were included. 5-year transplant-free survival was 42%, significantly worse than group 1 PH. A multivariable Cox proportional hazards model identified PVR, but not FEV1 as a major predictor of outcome. 418 patients (50%) received phosphodiesterase-5 inhibitor (PDE5i) therapy, which was associated with significantly reduced mortality: hazard ratio 0.65 [0.57,0.75] for the entire PH-COPD cohort and 0.83 [0.74,0.94] when performing landmark analysis. This PDE5i effect was robustly reproduced when performing subgroup analyses for patients with moderate/severe PH, various comorbidities, and supplemental oxygen requirement, and when assessing the impact of unobserved confounders. InterpretationPH-COPD patients exhibit poor transplant-free survival, with PVR being a predictor of mortality. In this meta-registry, PDE5i therapy was associated with a significant reduction in mortality across all tested models.

Dynamic Prediction Using Landmark Historical Functional Cox Regression

Dynamic prediction of survival data in the presence of time-varying covariates is an area of active research. Two common analytic approaches for this type of data are joint modeling of the longitudinal and survival processes and landmarking. However, there has been little work dedicated to densely measured time-varying covariates using either approach. Moreover, the software for joint modeling is slow, especially for large datasets, and rather limited for landmarking. We propose a landmark approach for dynamic prediction of survival outcomes using densely measured longitudinal predictors, which treats the past of the time-varying covariate at each landmark point as a functional predictor. This approach is orders of magnitude faster than existing software for simpler joint models. Our extensive comparative simulation study required 8.4 computation-years, over 99% of which was devoted to fitting and predicting from two joint models. Our landmark approach performs similarly to joint modeling when the joint model is correctly specified and substantially out-performs it when it is not. Methods are motivated by an application predicting time to recovery of Multiple Sclerosis lesions in a large neuroimaging dataset. Supplementary materials for this article are available online.

Accuracy is not enough: a heterogeneous ensemble model versus FGSM attack

AbstractIn this paper, based on facial landmark approaches, the possible vulnerability of ensemble algorithms to the FGSM attack has been assessed using three commonly used models: convolutional neural network-based antialiasing (A_CNN), Xc_Deep2-based DeepLab v2, and SqueezeNet (Squ_Net)-based Fire modules. Firstly, the three individual deep learning classifier-based Facial Emotion Recognition (FER) classifications have been developed; the predictions from all three classifiers are then merged using majority voting to develop the HEM_Net-based ensemble model. Following that, an in-depth investigation of their performance in the case of attack-free has been carried out in terms of the Jaccard coefficient, accuracy, precision, recall, F1 score, and specificity. When applied to three benchmark datasets, the ensemble-based method (HEM_Net) significantly outperforms in terms of precision and reliability while also decreasing the dimensionality of the input data, with an accuracy of 99.3%, 87%, and 99% for the Extended Cohn-Kanade (CK+), Real-world Affective Face (RafD), and Japanese female facial expressions (Jaffee) data, respectively. Further, a comprehensive analysis of the drop in performance of every model affected by the FGSM attack is carried out over a range of epsilon values (the perturbation parameter). The results from the experiments show that the advised HEM_Net model accuracy declined drastically by 59.72% for CK + data, 42.53% for RafD images, and 48.49% for the Jaffee dataset when the perturbation increased from A to E (attack levels). This demonstrated that a successful Fast Gradient Sign Method (FGSM) can significantly reduce the prediction performance of all individual classifiers with an increase in attack levels. However, due to the majority voting, the proposed HEM_Net model could improve its robustness against FGSM attacks, indicating that the ensemble can lessen deception by FGSM adversarial instances. This generally holds even as the perturbation level of the FGSM attack increases.

Evaluation of automatic cochlear dimension measurement using ALPACA: a comparative study

Background Cochlear dimension measurements are critical in diagnosing and managing congenital sensorineural hearing loss. Objectives To evaluate the feasibility and reliability of an automated landmark approach for measuring cochlear dimensions (A-, B- and H-values). Material and Methods Cochlear parameters from 100 patients were measured by MPR, manual three-dimensional and ALPACA. We assessed intra- and inter-observer reliability as well as inter-method reliability. Statistical analyses were conducted to detect differences between the right and left ears, as well as to assess the relevance of the values obtained using ALPACA. Results All A-, B-, and H-values measured by the various methods showed a high intra-observer reliability with intra-class correlation coefficients (ICC) ranging from 0.70 to 0.99, and values gained by ALPACA reaching the highest ICC. Inter-method reliability was at a good level with ICC ranging from 0.51 to 0.86. There were no significant differences between the right and left ears’ measured values. Obvious positive correlations existed among cochlear dimensions measured by ALPACA. Conclusions and Significance The ALPACA method can be used to measure cochlear dimensions. Values obtained by the method demonstrate high reliability and consistency with a significant reduction in intra-observer variability compared to results from conventional MPR and manual 3D measurements.

Impact of systemic disease on CNS disease control after stereotactic radiosurgery to breast cancer brain metastases (The SYBRA Study)

The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS [LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46–6.83, p = 0.0034; LM2: 5.32, 2.33–12.15, p = <0.0001] and shorter OS (LM1: HR with 95% CI 4.28, 1.98–9.12, p = 0.0002; LM2: 7.40, 3.10–17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.

Epidemiology of Diffuse Alveolar Hemorrhage in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk factors and outcomes are not well understood owing to a sparsity of cases spread across multiple centers. The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplantation-related risk factors and comorbid critical care diagnoses associated with post-HCT DAH. Retrospective analysis was performed in a multicenter cohort of 6995 patients age ≤21 years who underwent allogeneic HCT between 2008 and 2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox regression, with DAH as a time-varying covariate. DAH occurred in 81 patients at a median of 54 days post-HCT (interquartile range, 23 to 160 days), with a 1-year post-transplantation cumulative incidence probability of 1.0% (95% confidence interval [CI], .81% to 1.3%) and was noted in 7.6% of all pediatric intensive care unit patients. Risk factors included receipt of transplantation for nonmalignant hematologic disease (reference: malignant hematologic disease; hazard ratio [HR], 1.98; 95% CI, 1.22 to 3.22; P = .006), use of a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis (referent: CNI plus methotrexate; HR, 1.89; 95% CI, 1.07 to 3.34; P = .029), and grade III-IV acute GVHD (HR, 2.67; 95% CI, 1.53-4.66; P < .001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (P < .05) than those without DAH. From the time of DAH, median survival was 2.2 months, and 1-year overall survival was 26% (95% CI, 17% to 36%). Among all HCT recipients, the development of DAH when considered was associated with a 7-fold increase in unadjusted all-cause post-HCT mortality (HR, 6.96; 95% CI, 5.42 to 8.94; P < .001). In a landmark analysis of patients alive at 2 months post-HCT, patients who developed DAH had a 1-year overall survival of 33% (95% CI, 18% to 49%), compared to 82% (95% CI, 81% to 83%) for patients without DAH (P < .001). Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of nonmalignant hematologic indication for HCT, use of CNI + MMF as GVHD prophylaxis, and severe acute GVHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes.

Dynamic Prediction of Overall Survival for Patients with Osteosarcoma: A Retrospective Analysis of the EURAMOS-1 Clinical Trial Data.

Current prediction models for patients with ostosarcoma are restricted to predictions from a single, static point in time, such as diagnosis or surgery. These approaches discard information which becomes available during follow-up and may have an impact on patient's prognosis. This study aims at developing a dynamic prediction model providing 5-year overall survival (OS) predictions from different time points during follow-up. The developed model considers relevant baseline prognostic factors, accounting for where appropriate time-varying effects and time-varying intermediate events such as local recurrence (LR) and new metastatic disease (NM). A landmarking approach is applied to 1965 patients with high-grade resectable osteosarcoma from the EURAMOS-1 trial (NCT00143030). Results show that LR and NM negatively affected 5-year OS (HRs: 2.634, 95% CI 1.845-3.761; 8.558, 95% CI 7.367-9.942, respectively). Baseline factors with strong prognostic value (HRs > 2) included poor histological response (≥10% viable tumor), axial tumor location, and the presence of lung metastases. The effect of poor versus good histological response changed over time, becoming non-significant from 3.25 years post-surgery onwards. This time-varying effect, as well as the strong impact of disease-related time-varying variables, show the importance of including updated information collected during follow-up in the model to provide more accurate survival predictions.

Dengue viremia kinetics and effects on platelet count and clinical outcomes: An analysis of 2340 patients from Vietnam.

Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage. We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models. Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes. This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials. Wellcome Trust and European Union Seventh Framework Programme.

An unusual case of hoarseness of voice after left supraclavicular brachial plexus block

Supraclavicular brachial plexus block (SBPB) is a commonly used regional anesthetic technique for upper limb surgeries in orthopaedic patients. It provides intraoperative anesthesia and postoperative analgesia. SBPB can be administered using either a landmark approach or ultrasound guidance (USG). The use of ultrasound has reduced the complications associated with the block by providing excellent real-time visualization of the pleura, vessels, and plexus in relation to needle insertion. However, complications can still arise even with USG-guided block if a large volume of local anesthetics is used. In fact, a large volume is not necessary when performing USG-guided blocks.We report a case of a 25-year-old male who presented with hoarseness of voice after receiving a USG-guided supraclavicular block (left side) due to recurrent laryngeal nerve (RLN) block. While RLN block is more common in interscalene blocks, it is a rare complication in SBPB, with very few reported cases of hoarseness of voice due to RLN block after SBPB.

Development and internal validation of a dynamic fall risk prediction and monitoring tool in aged care using routinely collected electronic health data: a landmarking approach.

Falls pose a significant challenge in residential aged care facilities (RACFs). Existing falls prediction tools perform poorly and fail to capture evolving risk factors. We aimed to develop and internally validate dynamic fall risk prediction models and create point-based scoring systems for residents with and without dementia. A longitudinal cohort study using electronic data from 27 RACFs in Sydney, Australia. The study included 5492 permanent residents, with a 70%-30% split for training and validation. The outcome measure was the incidence of falls. We tracked residents for 60 months, using monthly landmarks with 1-month prediction windows. We employed landmarking dynamic prediction for model development, a time-dependent area under receiver operating characteristics curve (AUROCC) for model evaluations, and a regression coefficient approach to create point-based scoring systems. The model identified 15 independent predictors of falls in dementia and 12 in nondementia cohorts. Falls history was the key predictor of subsequent falls in both dementia (HR 4.75, 95% CI, 4.45-5.06) and nondementia cohorts (HR 4.20, 95% CI, 3.87-4.57). The AUROCC across landmarks ranged from 0.67 to 0.87 for dementia and from 0.66 to 0.86 for nondementia cohorts but generally remained between 0.75 and 0.85 in both cohorts. The total point risk score ranged from -2 to 57 for dementia and 0 to 52 for nondementia cohorts. Our novel risk prediction models and scoring systems provide timely person-centered information for continuous monitoring of fall risk in RACFs. Embedding these tools within electronic health records could facilitate the implementation of targeted proactive interventions to prevent falls.

Randomized controlled trial on analgesic effect of pre-operative fascia iliaca compartment block in geriatric patients with hip fracture

Objective While most geriatric patients with hip fracture benefit from definitive operative treatment, pre-operative pain management is often overlooked. Conventional oral analgesics may provide suboptimal pain control, resulting in poor morbidity outcomes. Fascia iliaca compartment block (FICB) provides a more consistent analgesic effect. This study aims to provide high level local evidence on the effect of FICB in pre-operative pain control for these patients in Hong Kong. Materials and Methods This study was a double-blinded randomized controlled trial. Mentally competent geriatric patients with acute fracture hip, admitted to United Christian Hospital, were recruited to receive pre-operative FICB. The procedure was carried out by landmark approach with addition of ultrasonography-guidance. They were randomized into intervention group (receiving 0.25% levobupivacaine), and control group (receiving normal saline as placebo). Numeric Rating Scale of pain score (at rest, and on gentle movement) at different time intervals, timing of injection, systemic analgesic use, complications, and demographics were compared. Results Total 80 patients were recruited from July 2019 to September 2021 and randomized into intervention and control groups. Two patients in intervention group and 1 in control group were withdrawn due to development of delirium. Demographics of both groups were comparable. Pain score at rest was significantly lower at 12 h after injection in intervention group (41.4% reduction, p = 0.03). Pain score upon gentle movement was significantly lower in intervention group at 1 h (p = 0.01), 12 h (28.9% reduction, p = 0.003) and 24 h after injection (p = 0.01). There was no complication from the procedure documented. Total systemic analgesic use was similar in both groups. Conclusion FICB is an effective choice of pre-operative analgesia for geriatric hip fracture patients with good safety profile, especially in controlling pain induced by movement. It shall be considered as a routine practice for suitable patients.

The anatomical location of the great saphenous vein at the thigh and ankle: a neonatal cadaver study

Providing critically ill neonatal patients with parenteral nutrition, medication, fluids, and access to blood sampling is essential in intensive care units. One option for blood sampling is the great saphenous vein within the proximal thigh, and near the medial malleolus in neonates via ‘conventional’ landmark and ultrasound techniques. Practitioners in many countries still use the traditional landmark approach to locate the great saphenous vein in neonates, regardless of access to ultrasound. We aim to provide measurements that accurately describe the anatomy of the great saphenous vein in neonates to aid in cannulation success. The great saphenous vein was exposed in the proximal thigh and near the medial malleolus by reflecting the skin in 31 and 30 formalin-fixed neonate cadavers, respectively. Pins were placed at essential bony landmarks and soft tissue structures. The termination of the great saphenous vein within the proximal thigh can be located 6.8 ± 1.5 mm inferior to the inguinal ligament. The average shortest distance from the medial malleolus to the great saphenous vein was 4.3 mm, 2.0 mm anterior, and 3.1 mm superiorly. The diameter of the great saphenous vein in the proximal thigh and at the medial malleolus ranged between 1.4 mm and 1.6 mm, and 0.9 mm and 1.1 mm, respectively with a 95% confidence level. Our results provide a more accurate description to gain venous access through the great saphenous vein. However, if available, ultrasound should be used to locate and confirm the diameter of the great saphenous vein in the lower limb.

Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease

Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. We pooled data from six existing cohort studies from Canada, the Netherlands, the UK, and the USA. Patients with IBD and an indication for CRC surveillance were included if they underwent at least one follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modelling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. The surveillance cohorts comprised 3,731 patients, enrolled and followed-up in the time period 1973-2021, with a median follow-up of 5.7 years (26,336 patient-years of follow-up); 146 individuals were diagnosed with aCRN. The model contained eight predictors, with a cross-validation median c-statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals prior to clinical application.

A Comprehensive Study on Relative Distances of Hand Landmarks Approach for American Sign Language Gesture

A Comprehensive Study on Relative Distances of Hand Landmarks Approach for American Sign Language Gesture

Corticosteroid injection for carpal tunnel syndrome: A meta-analysis comparing ultrasound guided approach with landmark approach.

To assess and compare the clinical and functional outcomes of corticosteroid injections in patients with carpal tunnel syndrome, focusing on two different approaches: ultrasound-guided and landmark-guided. A systematic search was conducted in PubMed, Scopus and Embase databases for relevant studies published prior to 30th April 2023. Studies that were either randomized controlled trials or had a cohort design were included. The review assessed symptom severity, functional status, electrodiagnostic parameters, complications, need for surgical intervention, visual analogue score, and grip strength. Pooled effect sizes were reported as relative risk (RR) or weighted mean difference (WMD). A total of 8 articles were included. Compared to those that received steroid injection using landmark approach, those with ultrasound guided approach had lower symptom severity scale (SSS) score on Boston Carpal Tunnel Questionnaire (BCTQ) [WMD -0.50, 95% CI: -0.94, -0.07; I2=78.0%, N=7], lower risk of "any complications" [RR 0.58, 95% CI: 0.36, 0.93; I2= 22.9%, N=3] and lower risk of need for surgical intervention [RR 0.55, 95% CI: 0.34, 0.89; I2= 3.0%, N=2]. All other parameters were similar in the two groups i.e., functional status scale (FSS) score, visual analogue score (VAS) and grip strength. The electrophysiological findings were similar in the two groups. Findings suggest that ultrasound guided approach may be better than landmark guided approach especially in terms of alleviation of symptoms, reducing the risk of complications and need for surgical intervention. However, larger trials with long term follow up may provide conclusive evidence.

Dynamic prediction of survival using multivariate functional principal component analysis: A strict landmarking approach.

Dynamically predicting patient survival probabilities using longitudinal measurements has become of great importance with routine data collection becoming more common. Many existing models utilize a multi-step landmarking approach for this problem, mostly due to its ease of use and versatility but unfortunately most fail to do so appropriately. In this article we make use of multivariate functional principal component analysis to summarize the available longitudinal information, and employ a Cox proportional hazards model for prediction. Additionally, we consider a centred functional principal component analysis procedure in an attempt to remove the natural variation incurred by the difference in age of the considered subjects. We formalize the difference between a 'relaxed' landmarking approach where only validation data is landmarked and a 'strict' landmarking approach where both the training and validation data are landmarked. We show that a relaxed landmarking approach fails to effectively use the information contained in the longitudinal outcomes, thereby producing substantially worse prediction accuracy than a strict landmarking approach.

Individualized Dosing Patterns in the Treatment of Older Patients with Gastrointestinal Stromal Tumors: Results of a Registry-Based Observational National Cohort Study Including 871 Patients.

While the effectiveness of tyrosine kinase inhibitors (TKIs) seems similar in older patients with gastrointestinal stromal tumors (GIST) compared with younger patients, toxicities in older patients treated with TKIs more often lead to discontinuation of treatment. To better understand the age-related pharmacology and pharmacodynamic differences in patients with GIST treated with TKIs, the primary aim of this study was to evaluate TKI dosing patterns in older patients with GIST, while the secondary aims were to evaluate differences in imatinib trough plasma concentrations between age groups and to compare the overall survival (OS) in patients with and without dose reductions in all treatment lines in a palliative setting. Patients (18 years of age or older) with histologically proven GIST diagnosed between January 2009 and June 2021 and treated with one or more lines of TKIs were selected from the Dutch GIST Registry (DGR) database. Age groups were divided into younger patients (age <70 years) and older patients (age ≥70 years). All imatinib trough plasma concentrations of blood withdrawals taken from initiation of imatinib until a maximum of 1 year of treatment with imatinib were collected. Reasons for first adjustment of treatment were classified as adverse event, dose modification, progressive disease and other reasons. The next treatment steps after first adjustment of treatment were defined as dose escalation, dose reduction, dose interruption, or end of treatment. The association of dose reduction and OS was analyzed using the landmark approach. Overall, 871 patients were included in this study, including 577 younger patients and 294 older patients. Older patients more often had an adverse event as the reason for first adjustment of treatment with both imatinib (45.6%; p<0.001) and sunitinib (58.6%; p=0.224) compared with younger patients (19.5% and 42.7%, respectively). Adjustment of imatinib and sunitinib after starting on a standard dose because of an adverse event most often resulted in dose reduction in both age groups. Median trough plasma concentrations of all samples taken within the first year after initiation of imatinib were higher in older patients (1228ng/mL, interquartile range [IQR] 959-1687) compared with younger patients (1035ng/mL [IQR 773-1377]; p<0.001). No significant differences were seen between OS in patients with or without dose reduction in all treatment lines (imatinib: p=0.270; sunitinib: p=0.547; and regorafenib: p=0.784). Older patients showed higher imatinib trough plasma concentrations compared with younger patients and also had earlier and more often adverse events as the reason for first adjustment of treatment with imatinib followed by dose reduction. However, in a landmark analysis, patients with imatinib dose reductions had no poorer outcomes compared with patients not requiring a dose reduction.