Artificial intelligence as a prediction tool for orthognathic surgery assessment.

INTRODUCTION: An ideal orthodontic treatment involves qualitative and quantitative measurements of dental and skeletal components to evaluate patients' discrepancies, such as facial, occlusal, and functional characteristics. Deciding between orthodontics and orthognathic surgery remains challenging, especially in borderline patients. Advances in technology are aiding clinical decisions in orthodontics. The increasing availability of data and the era of big data enable the use of artificial intelligence to guide clinicians' diagnoses. This study aims to test the capacity of different machine learning (ML) models to predict whether orthognathic surgery or orthodontics treatment is required, using soft and hard tissue cephalometric values. METHODS: A total of 920 lateral radiographs from patients previously treated with either conventional orthodontics or in combination with orthognathic surgery were used, comprising n = 558 Class II and n = 362 Class III patients, respectively. Thirty-two measures were obtained from each cephalogram at the initial appointment. The subjects were randomly divided into training (n = 552), validation (n = 183), and test (n = 185) datasets, both as an entire sample and divided into Class II and Class III sub-groups. The extracted data were evaluated using 10 machine learning models and by a four-expert panel consisting of orthodontists (n = 2) and surgeons (n = 2). RESULTS: The combined prediction of 10 models showed top-ranked performance in the testing dataset for accuracy, F1-score, and AUC (entire sample: 0.707, 0.706, 0.791; Class II: 0.759, 0.758, 0.824; Class III: 0.822, 0.807, 0.89). CONCLUSIONS: The proposed combined 10 ML approach model accurately predicted the need for orthognathic surgery, showing better performance in Class III patients.

Physician estimate of inflammation vs global assessment in explaining variations in swollen joint counts in rheumatoid arthritis patients.

Objective: To analyse patients with RA for inflammatory activity by physician estimate of global assessment (DOCGL) vs an estimate of inflammatory activity (DOCINF) to explain variation in the swollen joint count (SJC). Methods: Patients with RA were studied at routine care visits. Patients completed a multidimensional health assessment questionnaire (MDHAQ) and the physician completed a 28-joint count for swollen (SJC), tender (TJC) and deformed (DJC) joints and a RheuMetric checklist with a 0-10 DOCGL visual numeric scale (VNS) and 0-10 VNS estimates of inflammation (DOCINF), damage (DOCDAM) and patient distress (DOCSTR). The disease activity score in 28 joints with ESR (DAS28-ESR), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were calculated. Individual scores and RA indices were compared according to Spearman correlation coefficients and regression analyses. Results: A total of 104 unselected patients were included, with a median age and disease duration of 54.5 and 5 years, respectively. The median DAS28-ESR was 2.9 (Q1-Q3: 2.0-3.7), indicating low activity. DOCINF was correlated significantly with DOCGL (ρ = 0.775). Both DOCGL and DOCINF were correlated significantly with most other measures; correlations with DOCGL were generally higher than with DOCINF other than for SJC. In regression analyses, DOCINF was more explanatory of variation in SJC than DOCGL and other DAS28-ESR components. Conclusions: Variation in SJC is explained more by a 0-10 DOCINF VNS than the traditional DOCGL or any other measure in RA patients seen in routine care. DOCINF on a RheuMetric checklist can provide informative quantitative scores concerning inflammatory activity in RA patients monitored over long periods.

Elevated DAS28-ESR in patients with rheumatoid arthritis who have comorbid fibromyalgia is associated more with tender joint counts than with patient global assessment or swollen joint counts: implications for assessment of inflammatory activity.

OBJECTIVES: More than 20% of rheumatoid arthritis (RA) patients have comorbid fibromyalgia (FM+), which may elevate DAS28-ESR (disease activity score 28-erythrocyte sedimentation rate) and other indices, resulting in challenges to assess inflammatory disease activity. Although several reports indicate that elevated patient global assessment (PATGL) may elevate DAS28 in the absence of inflammatory activity, less information is available concerning the other three components, tender joint count (TJC), swollen joint count (SJC), and erythrocyte sedimentation rate (ESR), to possibly elevate DAS28 in FM+ vs. FM- RA patients. METHODS: A PubMed search identified 14 reports which presented comparisons of DAS28-ESR and its four components in RA FM+ vs. FM- groups. Median DAS28, component arithmetic differences, pooled effect sizes and 95% confidence intervals were analysed in the FM+ vs. FM- groups. RESULTS: In FM+ vs. FM- groups, median DAS28 was 5.3 vs. 4.2, SJC 4.0 vs. 3.0, TJC 13.2 vs. 5.3, PATGL 61.6 vs. 39.9, ESR 26.3 vs. 26.5. DAS28-ESR was classified as "high" (>5.1) in 11/14 FM+ groups and "moderate" (3.2-5.1) in all 14 FM- groups. Effect sizes in FM+ vs. FM- groups for DAS28-ESR, SJC, TJC, PATGL, and ESR were large (≥0.8) in 10/14, 1/13, 12/13, 7/13, and 1/13 comparisons, respectively, and pooled effect sizes 0.84 (0.3, 1.4), 0.33 (-0.4, 1.0), 1.27 (0.01, 2.5), 0.91 (-0.6, 2.4), and 0.07 (-0.6, 0.7), respectively. CONCLUSIONS: DAS28-ESR is elevated significantly in FM+ vs. FM- RA patients; pooled effect sizes were highest for TJC, followed by PATGL, SJC and ESR. The findings appear relevant to response and remission criteria, treat-to-target, and general management of RA.

A Comparison of Statistical Methods to Construct Confidence Intervals and Fiducial Intervals for Measures of Health Disparities.

Health disparities are differences in health status across different socioeconomic groups. Classical methods, e.g., the Delta method, have been used to estimate the standard errors of estimated measures of health disparities and to construct confidence intervals for these measures. However, the confidence intervals constructed using the classical methods do not have good coverage properties for situations involving sparse data. In this article, we introduce three new methods to construct fiducial intervals for measures of health disparities based on approximate fiducial quantities. Through a comprehensive simulation study, We compare the empirical coverage properties of the proposed fiducial intervals against two Monte Carlo simulation-based methods-utilizing either a truncated Normal distribution or the Gamma distribution-as well as the classical method. The findings of the simulation study advocate for the adoption of the Monte Carlo simulation-based method with the Gamma distribution when a unified approach is sought for all health disparity measures.

PROMIS-29 in rheumatoid arthritis patients who screen positive or negative for fibromyalgia on MDHAQ FAST4 (fibromyalgia assessment screening tool) or 2011 fibromyalgia criteria.

BACKGROUND: PROMIS-29 T-scores query health-related quality of life (HRQL) in 7 domains, physical function, pain, fatigue, anxiety, depression, sleep quality, and social participation, to establish population norms. An MDHAQ (multidimensional health assessment questionnaire) scores these 7 domains and includes medical information such as a FAST4 (fibromyalgia assessment screening tool) index. We analyzed PROMIS-29 T-scores in rheumatoid arthritis (RA) patients vs population norms and for positive vs negative fibromyalgia (FM) screens and compared PROMIS-29 T-scores to MDHAQ scores to assess HRQL. METHODS: A cross-sectional study was performed at one routine visit of 213 RA patients, who completed MDHAQ, PROMIS-29, and reference 2011 FM Criteria. PROMIS-29 T-scores were compared in RA vs population norms and in FM+ vs FM- RA patients, based on MDHAQ/FAST4 and reference criteria. Possible associations between PROMIS-29 T-scores and corresponding MDHAQ scores were analyzed using Spearman correlations and multiple regressions. RESULTS: Median PROMIS-29 T-scores indicated clinically and statistically significantly poorer status in 26-29% FM+ vs FM- RA patients, with larger differences than in RA patients vs population norms for 6/7 domains. MDHAQ scores were correlated significantly with each of 7 corresponding PROMIS-29 domains (|rho|≥0.62, p<0.001). Linear regressions explained 55-73% of PROMIS-29 T-score variation by MDHAQ scores and 56%-70% of MDHAQ score variation by PROMIS-29 T-scores. CONCLUSIONS: Scores for 7 PROMIS-29 domains and MDHAQ were highly correlated. The MDHAQ is effective to assess HRQL and offers incremental medical information, including FAST4 screening. The results indicate the importance of assessing comorbidities such as fibromyalgia screening in interpreting PROMIS-29 T-scores.

Analysing the Effect of Energy Intensity on Carbon Emission Reduction in Beijing.

Beijing has experienced rapid economic development since the reforms and opening up. However, the traditional development model based on excessive energy consumption has posed great challenges to the ecological environment. To curb environmental degradation and achieve sustainable social development, Beijing has proposed to achieve carbon neutrality by 2050. As an important indicator of energy consumption, it is necessary to clarify how energy intensity (EI) affects carbon emissions (CE) to achieve carbon neutrality in Beijing by 2050. This study first decomposes the drivers of CE in Beijing from 2010 to 2020 using the logarithmic mean Divisia index (LMDI) method and comparatively analyses the impact of EI on CE. Then, the spatial Dubin model (SDM) is used to analyse the spatial spillover effect of EI on CE at the regional level. Finally, the macro moderating role of economic development in the effect of EI on CE is analysed. The results show that the effect of EI has been the main driver of CE reduction in Beijing. Among the industrial sectors, manufacturing and transportation have had the greatest success in reducing CE through EI reduction. At the regional level, there is a spatial spillover effect of EI on CE, and the effect of carbon reduction through the spillover effect of EI is greater than the direct effect of EI. Economic factors have an enhanced moderating effect on the process of EI affecting CE, and this moderating effect has threshold properties.

Patient global assessment is elevated by up to 5 of 10 units in patients with inflammatory arthritis who screen positive for fibromyalgia (by FAST4) and/or depression (by MDS2) on a single MDHAQ.

BACKGROUND: Patient global assessment (PATGL) is a component of rheumatoid arthritis (RA) and spondyloarthritis (SpA) activity indices, reflecting inflammation in selected clinical trial patients. In routine care, PATGL often may be elevated independently of inflammatory activity by fibromyalgia (FM) and/or depression, leading to complexities in interpretation. A feasible method to screen for FM and/or depression could help to clarify interpretation of high PATGL and index scores, including explanation of apparent limited responses to anti-inflammatory therapies. PATIENTS AND METHODS: Patients with RA or SpA in routine care in Barcelona, Chicago, and Sydney complete a 2-page multidimensional health assessment questionnaire (MDHAQ) in 5-10 min. The MDHAQ includes PATGL and three indices, RAPID3 (routine assessment of patient index data) to assess clinical status, FAST4 (0-4 fibromyalgia assessment screening tool) and MDS2 (0-2 MDHAQ depression screen). PATGL was compared for each diagnosis at each site and pooled data in FAST4 positive (+) vs negative (-) and/or MDS2+ vs MDS2- patients using medians and median regressions. RESULTS: Median PATGL was 5.0 in 393 RA and 175 SpA patients; 2.0-3.0 in 305 (58.9%) FAST4-,MDS2- patients, 5.5-6.0 in 71 (13.7%) FAST4-,MDS2+ patients, 7.0-7.5 in 50 (9.7%) FAST4+,MDS2- patients, and 7.0-8.0 in 92 (17.8%) FAST4+,MDS2+ patients. Positive FAST4 and/or MDS2 screens were seen in 41% of patients. Results were similar in RA and SpA at 3 settings on 3 continents. CONCLUSION: Median 0-10 PATGL varied from 2-3/10 to 5.5-8/10, according to negative vs positive screening for FM and/or depression on a single MDHAQ for busy clinical settings.

Economical irregular silica as an effective dispersive solid-phase extraction sorbent for the quantification of calcitriol in soft capsules.

Calcitriol is an active product of vitamin D produced by the liver and kidney hydroxylase metabolism with strong physiological activity. It is the preferred form of medicine for patients with insufficient bone mineralization due to chronic kidney disease. Calcitriol soft capsule is one of the common preparation forms, the main drug content of which is very low (1.55 µg g-1), and the pharmaceutical excipients interfere greatly, especially the oily matrix medium-chain triglycerides. Therefore, removing the interference of oily matrix is ​​the main challenge in the content determination. At present, the commonly used sample purification method for the determination of calcitriol in soft capsules is liquid-liquid extraction, but it usually consumes a lot of toxic organic solvents and it is costly. The adoption of SPE purification method, on the one hand, requires specific experimental equipment, and on the other hand, the organic solvent used in the experiment may cause the dissolution of SPE column tube materials, which will interfere with the subsequent detection. Herein, in order to achieve a cost-effective and reliable determination of calcitriol soft capsule content, we developed a dispersive solid-phase (DSPE) extraction method that directly uses irregular silica as sorbent, which is followed by high-performance liquid chromatography equipped with a UV detector(HPLC-UV)analysis. Selective retention of calcitriol is achieved by the polar interaction between calcitriol and silica, what's more, sufficient contact between washing solvent and sorbent can be guaranteed. Therefore, after pretreatment with DSPE, the interference of oily matrix on detection can be mostly removed and then improve the accuracy of the method compared to the SPE method. Under the optimal conditions of DSPE, calcitriol showed a good linear relationship in the range of 0.15-2.99 µg g-1, the R2 was 0.997. Satisfactory recoveries ranging from 101.1%-102.0% for calcitriol were achieved in the oily matrix at the levels of 0.75, 1.50 and 2.24 µg g-1. And the intra-day and inter-day RSD were less than 2.5 % and 3.2 %. Meanwhile, the LOD and LOQ of calcitriol was 0.01 µg g-1 and 0.02 µg g-1, which is in full compliance with the regulatory level fixed by the EU, China or other countries. This method was further verified to determine the content of calcitriol in commercial calcitriol soft capsules and the recoveries of three batches of products was 86.2 %-94.4 %. Based on these characteristics, the proposed method makes it possible to determine the low content of weakly polar drugs in the oily matrix in a simple, low-cost and reliable way.

Multidimensional Health Assessment Questionnaire as an Effective Tool to Screen for Depression in Routine Rheumatology Care.

OBJECTIVE: To analyze the use of the Multidimensional Health Assessment Questionnaire (MDHAQ) to screen for depression, as compared to 2 reference standards, the Patient Health Questionnaire 9 (PHQ-9) and the Hospital Anxiety and Depression Scale depression domain (HADS-D). METHODS: Patients from Barcelona with a primary diagnosis of rheumatoid arthritis (RA) or spondyloarthritis (SpA) completed the MDHAQ, the PHQ-9 (depression ≥10), and the HADS-D (depression ≥8) measures. The MDHAQ includes 2 depression items, 1 in the patient-friendly HAQ, scored in a 4-point format from 0 to 3.3, and a yes/no item on a 60-symptom checklist. Percentage agreement and kappa statistics quantified the agreement between 6 screening criteria: yes on the 60-symptom checklist, a score of ≥1.1, a score of ≥2.2 on a 4-point scale, and either a response of yes on the 60-symptom checklist or scores of ≥2.2, PHQ-9 ≥10, and HADS-D ≥8. RESULTS: Depression screening was positive according to 6 criteria in 19.6-32.4% of 102 patients with RA, and 27.9-44.8% of 68 with SpA (total = 170). All MDHAQ scores, including depression items, were higher in patients with SpA compared to patients with RA, and within each diagnostic group in patients who met PHQ-9 ≥10 and HADS-D ≥8 depression screening criteria. The highest percentage agreement between an MDHAQ screening criterion versus PHQ-9 ≥10 was 83.3% for either an answer of yes on the 60-symptom checklist or a score of ≥2.2 on a 4-point scale, which we have termed MDHAQ-Dep. The agreement of MDHAQ-Dep versus HADS-D ≥8 was 81.7%, similar to the agreement of PHQ-9 ≥10 versus HADS-D ≥8, which was 82.2%. Kappa measures of agreement were 0.63 for MDHAQ-Dep versus PHQ-9 ≥10, 0.60 for MDHAQ-Dep versus HADS-D ≥8, and 0.62 for PHQ-9 ≥10 versus HADS-D ≥8. CONCLUSION: A positive MDHAQ-Dep response (either an answer of yes on a 60-symptom checklist or a score of ≥2.2 on a 4-point scale) yielded similar results to PHQ-9 ≥10 or HADS-D ≥8 to screen for depression in these RA and SpA patients.

Analysis of secondary phenotypes in multigroup association studies.

Although case-control association studies have been widely used, they are insufficient for many complex diseases, such as Alzheimer's disease and breast cancer, since these diseases may have multiple subtypes with distinct morphologies and clinical implications. Many multigroup studies, such as the Alzheimer's Disease Neuroimaging Initiative (ADNI), have been undertaken by recruiting subjects based on their multiclass primary disease status, while extensive secondary outcomes have been collected. The aim of this paper is to develop a general regression framework for the analysis of secondary phenotypes collected in multigroup association studies. Our regression framework is built on a conditional model for the secondary outcome given the multigroup status and covariates and its relationship with the population regression of interest of the secondary outcome given the covariates. Then, we develop generalized estimation equations to estimate the parameters of interest. We use both simulations and a large-scale imaging genetic data analysis from the ADNI to evaluate the effect of the multigroup sampling scheme on standard genome-wide association analyses based on linear regression methods, while comparing it with our statistical methods that appropriately adjust for the multigroup sampling scheme. Data used in preparation of this article were obtained from the ADNI database.

Investigation of a potential drug-drug interaction between salbutamol and ambroxol and bioequivalence of a new fixed-dose combination containing these two drugs in healthy Chinese subjects.

OBJECTIVES: The aims of the study were to investigate the potential drug-drug interaction between salbutamol and ambroxol, the bioequivalence of the new fixed-dose combination containing salbutamol and ambroxol compared with co-administration of the two separate formulations, and to describe the safety and tolerability of the fixed-dose combination formulation in healthy Chinese volunteers. MATERIALS AND METHODS: An open-label, single-dose, four-treatment, four-period crossover study for evaluation of drug-drug interaction and bioequivalence (n = 24) was performed. Each participant received salbutamol 4 mg, ambroxol 15 mg, salbutamol 4 mg co-administered with ambroxol 15 mg or fixed-dose combination formulation (salbutamol 4 mg and ambroxol 15 mg). Plasma concentrations of two analytes were determined with the use of validated LC-MS/MS method. Safety and tolerability were assessed by recording adverse events. RESULTS: Co-administration of salbutamol and ambroxol was not associated with a significant influence on single salbutamol or ambroxol pharmacokinetics. After statistical comparisons of log-transformed Cmax and AUC of salbutamol and ambroxol between fixed-dose combination and concomitant treatments, all 90% confidence intervals of geometric mean ratios were within the predefined equivalence range of 80 - 125%. No serious adverse events were reported, and all treatments were safe and well tolerated in Chinese healthy subjects. CONCLUSION: There were no significant drug-drug pharmacokinetic interactions between salbutamol and ambroxol after oral administration. The new formulation was bioequivalent to the co-administration of two drugs in separate dosage forms.
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Perfusion-weighted magnetic resonance imaging in the assessment of haemodynamics following stent angioplasty in patients with symptomatic middle cerebral artery plaque stenosis at the M1 segment.

The most effective strategy to assess changes in the brain haemodynamics of stent angioplasty in patients with symptomatic ischemia of the M1 segment of the middle cerebral artery (MCA) remains unknown. The purpose of the present study was to use perfusion-weighted magnetic resonance imaging (PWI) to evaluate the effect of stent angioplasty in treating patients with symptomatic MCA plaque stenosis. Stent angioplasty was performed on 23 patients with reduplicative transient ischaemic attack who were refractory to medical therapy. All patients had MCA plaque stenosis at the M1 segment. Brain PWI was obtained from four major regions of interest (ROIs) at the frontal parietal, temporal, lateral ventricle and basal ganglia lobes prior to and following stent implantation. In addition, cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT) and time to peak (TTP) parameters derived from PWI were calculated. All patients underwent digital subtraction angiography following surgery to confirm the patency. Computed tomography angiography or PWI was performed 1 week and 3 months post-surgery. According to pre-operative PWI, there was significant hypoperfusion in the symptomatic frontal parietal, temporal, lateral ventricle and basal ganglia lobes. By contrast, the regional CBF and CBF increased in the ROIs of the affected cerebral hemisphere 3 months after stent implantation (P<0.05 vs. pre-operative data). Additionally, post-operative MTT and TTP in the ROIs on the operative side were significantly shorter than pre-operative MTT and TTP (P<0.05). During the follow-up period, the frequency of transient ischaemic attack was reduced or disappeared in all patients during the follow-up. In conclusion, PWI enables an effective and objective assessment of haemodynamics prior to and following stent angioplasty in patients with plaque stenosis of MCA at the M1 segment.