Contrast-specific propensity scores for causal inference with multiple interventions.

Existing methods that use propensity scores for heterogeneous treatment effect estimation on non-experimental data do not readily extend to the case of more than two treatment options. In this work, we develop a new propensity score-based method for heterogeneous treatment effect estimation when there are three or more treatment options, and prove that it generates unbiased estimates. We demonstrate our method on a real patient registry of patients in Singapore with diabetic dyslipidemia. On this dataset, our method generates heterogeneous treatment recommendations for patients among three options: Statins, fibrates, and non-pharmacological treatment to control patients' lipid ratios (total cholesterol divided by high-density lipoprotein level). In our numerical study, our proposed method generated more stable estimates compared to a benchmark method based on a multi-dimensional propensity score.

Efficient Tin-Based Perovskite Solar Cell with a Cesium Acetate Pre-buried PEDOT:PSS Hole Transport Layer.

The strong Lewis acid tin halide leads to an excessively fast crystallization rate, resulting in more defects in the film and degraded device performance. In this work, a cesium acetate (CsAc) pre-buried poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hole transport layer acts as nucleation points during the crystallization of tin-based perovskite, which can induce preferential orientation growth of crystals and increase the grain size to improve the quality of crystallization. The addition of CsAc not only can increase the conductivity of PEDOT:PSS but also can improve the wettability of the perovskite precursor solution to enhance the interface contact between the hole transport layer and perovskite layer. Because of the incorporation of CsAc in PEDOT:PSS, the average short-circuit current density increases from 23.80 to 27.60 mA cm-2. Furthermore, a power conversion efficiency of 10.99% is achieved for a tin-based perovskite solar cell with CsAc-doped PEDOT:PSS as the hole transport layer.

Feasibility analysis of a prevention programme for patients with early chronic disease using A mathematical model.

The increasing prevalence of the chronic disease is of considerable concern to health-care organisations. Prevention programmes to patients with early chronic disease have the potential to improve individual health and quality of life through disease avoidance or delay and to save the medical cost of the health care system. Due to the limited budget in healthcare this study seeks to analyse the feasibility of a programme prior to implementation. A mathematical model is developed to determine incidence reduction rate at which the underlying cost break-even can be achieved; consequently, the programme would be feasible. We show the existence and uniqueness of the underlying incidence reduction and establish the feasibility frontier concerning the trade-offs between intervention effective period and incidence reduction rate. We use a diabetes prevention programme to demonstrate the efficiency and advantage of the model. The proposed model would inform decision-makers scientific principles in determining an intervention for implementation.

CD-Surv: a contrastive-based model for dynamic survival analysis.

Survival analysis, aimed at investigating the relationships between covariates and event time, has exhibited profound effects on health service management. Longitudinal data with sequential patterns, such as electronic health records (EHRs), contain a large volume of patient treatment trajectories, and therefore, provide great potential for survival analysis. However, most existing studies address the survival analysis problem in a static manner, that is, they only utilize a fraction of longitudinal data, ignore the correlations between multiple visits, and usually may not be able to capture the latent representations of patient treatment trajectories. This inevitably deteriorates the performance of the survival analysis. To address this challenge, we propose an end-to-end contrastive-based model CD-Surv to better understand the patient treatment trajectories and dynamically predict the survival probability of a target patient. Specifically, two data augmentation strategies, namely, mask generation and shuffle generation, are adopted to augment the real treatment trajectories documented in the EHR. Based on this, the hidden representations of the real trajectories can be improved by utilizing contrastive learning between augmented and real trajectories. We evaluated our proposed CD-Surv on two real-world datasets, and the experimental results indicated that our proposed model could outperform state-of-the-art baselines on various evaluation metrics.

Random plasma glucose levels and cause-specific mortality among Chinese adults without known diabetes: an 11-year prospective study of 450,000 people.

INTRODUCTION: We examined the associations between long-term usual random plasma glucose (RPG) levels and cause-specific mortality risks among adults without known diabetes in China. RESEARCH DESIGN AND METHODS: The China Kadoorie Biobank recruited 512,891 adults (59% women) aged 30-79 from 10 regions of China during 2004-2008. At baseline survey, and subsequent resurveys of a random subset of survivors, participants were interviewed and measurements collected, including on-site RPG testing. Cause of death was ascertained via linkage to local mortality registries. Cox regression yielded adjusted HR for all-cause and cause-specific mortality associated with usual levels of RPG. RESULTS: During median 11 years' follow-up, 37,214 deaths occurred among 452,993 participants without prior diagnosed diabetes or other chronic diseases. There were positive log-linear relationships between RPG and all-cause, cardiovascular disease (CVD) (n=14,209) and chronic kidney disease (CKD) (n=432) mortality down to usual RPG levels of at least 5.1 mmol/L. At RPG <11.1 mmol/L, each 1.0 mmol/L higher usual RPG was associated with adjusted HRs of 1.14 (95% CI 1.12 to 1.16), 1.16 (1.12 to 1.19) and 1.44 (1.22 to 1.70) for all-cause, CVD and CKD mortality, respectively. Usual RPG was positively associated with chronic liver disease (n=547; 1.45 (1.26 to 1.66)) and cancer (n=12,680; 1.12 (1.09 to 1.16)) mortality, but with comparably lower risks at baseline RPG ≥11.1 mmol/L. These associations persisted after excluding participants who developed diabetes during follow-up. CONCLUSIONS: Among Chinese adults without diabetes, higher RPG levels were associated with higher mortality risks from several major diseases, with no evidence of apparent thresholds below the cut-points for diabetes diagnosis.

Consumption of Tea, Alcohol, and Fruits and Risk of Kidney Stones: A Prospective Cohort Study in 0.5 Million Chinese Adults.

A few prospective studies have suggested that tea, alcohol, and fruit consumption may reduce the risk of kidney stones. However, little is known whether such associations and their combined effect persist in Chinese adults, for whom the popular tea and alcohol drinks are different from those investigated in the aforementioned studies. The present study included 502,621 participants from the China Kadoorie Biobank (CKB). Information about tea, alcohol, and fruit consumption was self-reported at baseline. The first documented cases of kidney stones during follow-up were collected through linkage with the national health insurance system. Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). During a median of 11.1 years of follow-up, we collected 12,407 cases of kidney stones. After multivariable adjustment, tea, alcohol, and fruit consumption were found to be negatively associated with kidney stone risk, but the linear trend was only found in tea and fruit consumption. Compared with non-tea consumers, the HR (95% CI) for participants who drank ≥7 cups of tea per day was 0.73 (0.65-0.83). Compared with non-alcohol consumers, the HR (95% CI) was 0.79 (0.72-0.87) for participants who drank pure alcohol of 30.0-59.9 g per day but had no further decrease with a higher intake of alcohol. Compared with less-than-weekly consumers, the HR (95% CI) for daily fruit consumers was 0.81 (0.75-0.87). Even for those who did not drink alcohol excessively, increasing tea and fruit consumption could also independently reduce the stone risk. Among Chinese adults, tea, alcohol, and fruit consumption was associated with a lower risk of kidney stones.

Interconversion of Plasma Free Thyroxine Values from Assay Platforms with Different Reference Intervals Using Linear Transformation Methods.

Clinicians often encounter thyroid function tests (TFT) comprising serum/plasma free thyroxine (FT4) and thyroid stimulating hormone (TSH) measured using different assay platforms during the course of follow-up evaluations which complicates reliable comparison and interpretation of TFT changes. Although interconversion between concentration units is straightforward, the validity of interconversion of FT4/TSH values from one assay platform to another with different reference intervals remains questionable. This study aims to establish an accurate and reliable methodology of interconverting FT4 by any laboratory to an equivalent FT4 value scaled to a reference range of interest via linear transformation methods. As a proof-of-concept, FT4 was simultaneously assayed by direct analog immunoassay, tandem mass spectrometry and equilibrium dialysis. Both linear and piecewise linear transformations proved relatively accurate for FT4 inter-scale conversion. Linear transformation performs better when FT4 are converted from a more accurate to a less accurate assay platform. The converse is true, whereby piecewise linear transformation is superior to linear transformation when converting values from a less accurate method to a more robust assay platform. Such transformations can potentially apply to other biochemical analytes scale conversions, including TSH. This aids interpretation of TFT trends while monitoring the treatment of patients with thyroid disorders.

Social listening - revealing Parkinson's disease over day and night.

BACKGROUND: Nocturnal symptoms in Parkinson's disease are often treated after management of daytime manifestations. In order to better understand the unmet needs of nocturnal symptoms management, we analyzed the characteristics and burden of nocturnal symptoms from patients' perspectives and explored their changes over time. Overall symptoms (occurring at day or night) were collected to compare whether the unmet needs related to nocturnal symptoms and to overall symptoms are different. METHODS: We used a Social Listening big-data technique to analyze large amounts of Parkinson's disease symptoms in dialogues available from social media platforms in 2016 to 2018. These symptoms were classified as either overall symptoms or nocturnal symptoms. We used share of voice (SOV) of symptoms as a proportion of total dialogues per year to reflect the characteristics of symptoms. Negative sentiment score of symptoms was analyzed to find out their related burden. RESULTS: We found the SOV for overall motor symptoms was 79% and had not increased between 2016 and 2018 (79%, p = 0.5). The SOV for non-motor symptoms was 69% and had grown by 7% in 2018 (p <  0.01). The SOV for motor complications was 9% and had increased by 6% in 2018 (p <  0.01). The SOV of motor symptoms was larger than non-motor symptoms and motor complications (p <  0.01). The SOV of non-motor symptoms was larger than motor complications (p <  0.01). For nocturnal symptoms, 45% of the analyzed PD population reported nocturnal symptoms in 2018, growing by 6% (p <  0.01). The SOV for nocturnal-occurring motor symptoms was higher than most non-motor symptoms. However, non-motor symptoms had the higher increases and evoked higher negative sentiment regardless of whether they occurred during the day or night. For symptoms that can occur at either day or night, each nocturnal symptom was rated with a higher negative sentiment score than the same symptom during the day. CONCLUSIONS: The growing SOV and the greater negative sentiment of nocturnal symptoms suggest management of nocturnal symptoms is an unmet need of patients. A greater emphasis on detecting and treating nocturnal symptoms with 24-h care is encouraged.

Analysis via Markov decision process to evaluate glycemic control strategies of a large retrospective cohort with type 2 diabetes: the ameliorate study.

AIMS: Our aim was to explore optimal treatment decisions for HbA1c control for type 2 diabetes mellitus patients and assess the impact on potential improvements in quality of life compared with current guidelines. METHODS: We analyzed a large dataset of HbA1c levels, diabetes-related key risk factors and medication dispensed to 70,069 patients with type 2 diabetes from polyclinics and a large public hospital in Singapore during January 1, 2008, to December 31, 2015. A Markov decision process (MDP) model was developed to determine the optimal treatment policy concerning medication management for glycemic control over a long-term treatment period. We assessed the model performance by comparing quality-adjusted life years (QALYs) gained by the model with those derived by a conventional Markov model informed by current clinical guidelines. RESULTS: Numerical results showed that optimal treatment strategies derived by the MDP model could increase the total expected QALYs by as much as 0.27 years for patients at higher risk such as old age, high HbA1c levels and smokers. In particular, the improvements in QALYs gained for patients with HbA1c levels of 9% (75 mmol/mol) and above were higher than those with lower HbA1c levels. However, the potential improvements appeared to be marginal for patients at lower risk compared with current guidelines. CONCLUSIONS: Use of data-driven prescriptive analytics would help clinicians make evidence-based treatment decisions for HbA1c control for patients with type 2 diabetes, in particular for those at high risk.

Hyperthyroidism in the personalized medicine era: the rise of mathematical optimization.

Thyroid over-activity or hyperthyroidism constitutes a significant morbidity afflicting the world. The current medical practice of dose titration of anti-thyroid drug (ATD) treatment for hyperthyroidism is relatively archaic, being based on arbitrary and time-consuming trending of thyroid function that requires multiple clinic monitoring visits before an optimal dose is found. This prompts a re-examination into more deterministic and efficient treatment approaches in the present personalized medicine era. Our research project seeks to develop a personalized medicine model that facilitates optimal drug dosing via the titration regimen. We analysed 49 patients' data consisting of drug dosage, time period and serum free thyroxine (FT4). Ordinary differential equation modelling was applied to describe the dynamic behaviour of FT4 concentration. With each patient's data, an optimization model was developed to determine parameters of synthesis rate, decay rate and IC50. We derived the closed-form time- and dose-dependent solution which allowed explicit estimates of personalized predicted FT4. Our equation system involving time, drug dosage and FT4 can be solved for any variable provided the values of the other two are known. Compared against actual FT4 data within a tolerance, we demonstrated the feasibility of predicting the FT4 subsequent to any prescribed dose of ATD with favourable accuracy using the initial three to five patient-visits' data respectively. This proposed mathematical model may assist clinicians in rapid determination of optimal ATD doses within allowable prescription limits to achieve any desired FT4 within a specified treatment period to accelerate the attainment of euthyroid targets.

Personal ultraviolet Radiation exposure in a cohort of Chinese mother and child pairs: the Chinese families and children study.

BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

Physical activity, sedentary leisure-time and risk of incident type 2 diabetes: a prospective study of 512 000 Chinese adults.

Objective: Aim to examine the independent and joint associations of physical activity (PA) and sedentary leisure-time (SLT) with risk of diabetes and assess the extent to which these associations were mediated by adiposity. Research design and methods: The prospective China Kadoorie Biobank recruited ~512 000 adults from 10 diverse areas across China. Self-reported PA was estimated based on type, frequency and duration of specific types of PA, covering four domains (occupation, leisure, household and commuting). SLT was defined as hours per day spent watching television, reading or playing card games. Stratified Cox proportional hazards models were used to estimate adjusted HRs (aHRs) for PA and SLT associated with incident diabetes. Analyses were stratified by age-at-risk (5-year intervals), sex and region and adjusted for household income, education, alcohol consumption, smoking, fresh fruit intake, self-reported general health status, family history of diabetes and body mass index (BMI) status. Analyses of total PA, occupational and non-occupational PA and SLT were mutually adjusted for each other, as appropriate. Results: After ~9 years of follow-up, there were 14 940 incident diabetes cases among 460 736 participants without prior diabetes or cardiovascular diseases at baseline. The mean (SD) age at baseline was 51 (10.6) years, 59% were women and 43% resided in urban areas. Overall, the mean BMI was 23.5 (3.3) kg/m2, which differed by ~0.5 kg/m2 among individuals in the highest compared with the lowest PA and SLT groups. PA was inversely associated the risk of diabetes 16% (aHR: 0.84, 95% CI 0.81 to 0.88) lower in top than bottom fifth. After further adjustment for BMI this was attenuated to 0.99 (95% CI 0.98 to 1.00). SLT was positively associated with diabetes and each 1 hour per day higher usual level was associated with aHR of 1.13 (95% CI 1.09 to 1.17) for diabetes, attenuated to 1.05 (95% CI 1.01 to 1.09) after further adjustment for BMI. Conclusions: Among Chinese adults, higher levels of PA and lower levels of SLT were associated with lower risks of diabetes with no evidence of effect modification by each other. These associations appeared to arise mainly through adiposity.

Recognition of Schizophrenia with Regularized Support Vector Machine and Sequential Region of Interest Selection using Structural Magnetic Resonance Imaging.

Structural brain abnormalities in schizophrenia have been well characterized with the application of univariate methods to magnetic resonance imaging (MRI) data. However, these traditional techniques lack sensitivity and predictive value at the individual level. Machine-learning approaches have emerged as potential diagnostic and prognostic tools. We used an anatomically and spatially regularized support vector machine (SVM) framework to categorize schizophrenia and healthy individuals based on whole-brain gray matter densities estimated using voxel-based morphometry from structural MRI scans. The regularized SVM model yielded recognition accuracy of 86.6% in the training set of 127 individuals and validation accuracy of 83.5% in an independent set of 85 individuals. A sequential region-of-interest (ROI) selection step was adopted for feature selection, improving recognition accuracy to 92.0% in the training set and 89.4% in the validation set. The combined model achieved 96.6% sensitivity and 74.1% specificity. Seven ROIs were identified as the optimal discriminatory subset: the occipital fusiform gyrus, middle frontal gyrus, pars opercularis of the inferior frontal gyrus, anterior superior temporal gyrus, superior frontal gyrus, left thalamus and left lateral ventricle. These findings demonstrate the utility of spatial and anatomical priors in SVM for neuroimaging analyses in conjunction with sequential ROI selection in the recognition of schizophrenia.

Analysis of patient waiting time governed by a generic maximum waiting time policy with general phase-type approximations.

Waiting time can affect patient satisfaction and quality of care in the emergency department (ED). Studies have shown that waiting time accounted for more than 50 % of total patient turnaround time at ED. The objective of this study is to examine a maximum waiting time policy such that patients who would experience a long wait are assumed to be processed in a threshold period. In particular, we are interested to investigate the associated factors of the policy such as new mean waiting time and the threshold period and their interaction. Under the policy, original patient waiting distribution is transformed to a piecewise distribution where one piecewise discontinuous and one piecewise continuous distributions are further investigated. Under the phase-type (PH) distribution assumption on the original waiting time, we establish closed-form expressions concerning new mean waiting time and time points of the threshold period. By fitting PH distributions to patient waiting data of an emergency department in Singapore, the factors are then estimated under various scenarios using the obtained analytical expressions. Specifically, for a given target mean waiting time, the threshold period needed in the policy is estimated. New mean waiting time is assessed with different choices of the threshold period. Analytical expressions in terms of the variance of the transformed waiting time and the threshold period are also presented.

Clinical and radiological outcomes after treatment of sagittal fracture of mandibular condyle (SFMC) by using occlusal splint in children.

This study was designed to investigate the effects of occlusal splints in the treatment of sagittal fractures of the mandibular condyle in children. From January 1995 to December 2011, 37 sagittal fractures of the mandibular condyle in 30 patients aged 4-8 years old were included in this study. All the patients were treated with 1-2mm occlusal splints in the molar region. The mouths of the patients were kept slightly open by the occlusal splints for 3-6 months, and we reviewed the clinical and radiological remodelling of the affected condyles after treatment. Excellent (n=20) and good (n=10) clinical outcomes were achieved with full radiological remodelling seen in 19 and partial remodelling in 11. Treatment with occlusal splints is effective in delivering good results and function with minimal morbidity in children with sagittal fractures of the condyle, while permitting ongoing remodelling and growth in the short term.

The role of the lateral pterygoid muscle in the sagittal fracture of mandibular condyle (SFMC) healing process.

The aim of this study was to examine the role of the lateral peterygoid muscle in the reconstruction of the shape of the condyle during healing of a sagittal fracture of the mandibular condyle. Twenty adult sheep were divided into 2 groups: all had a unilateral operation on the right side when the anterior and posterior attachments of the discs were cut, and an oblique vertical osteotomy was made from the lateral pole of the condyle to the medial side of the condylar neck. Ten sheep had the lateral pterygoid muscle cut, and the other 10 sheep did not. Sheep were killed at 4 weeks (n=2 from each group), 12 weeks (n=4), and 24 weeks (n=4) postoperatively. Computed tomograms (CT) were taken before and after operations. We dissected the joints, and recorded with the naked eye the shape, degree of erosion, and amount of calcification of the temporomandibular joint (TMJ). In the group in which the lateral peterygoid muscle had not been cut the joints showed overgrowth of new bone and more advanced ankylosis. Our results show that the lateral pterygoid muscle plays an important part in reconstructing the shape of the condyle during the healing of a sagittal fracture of the mandibular condyle, and combined with the dislocated and damaged disc is an important factor in the aetiology of traumatic ankylosis of the TMJ.

Veterinary and radiological evaluations of open and closed treatment of type B diacapitular (intracapsular) fractures of the mandibular condyle in sheep.

The incidence of diacapitular (intracapsular) fractures of the mandibular condyle has increased in recent years, but their treatment remains inadequate, particularly of type B fractures. To evaluate and compare outcomes of open and closed treatments we created a sheep model of a type B fracture through an osteotomy. Eight sheep were randomly divided into two groups of four each to be given closed treatment or open reduction and internal fixation (ORIF) and were evaluated by veterinary and radiological examinations. Compared with before the osteotomy, there were significant reductions in maximum mouth opening (MMO) and left movement in the closed group, but no significant differences in the range of jaw movements in the ORIF group after 12 weeks of treatment. The two radiological scores that indicated the degree of osteoarthrotic changes and ankylosis of the temporomandibular joint (TMJ) in the ORIF group were significantly lower than those in the closed group. Anatomical observation confirmed the pathological changes in the right TMJ in the closed group and adaptive changes in the ORIF group. We conclude that ORIF is more efficient than closed treatment in restoring the function and shape of the TMJ to after a type B diacapitular condylar fracture.

Morphological evaluation of temporomandibular joint after open and closed treatment of type B diacapsular condylar fractures in sheep.

The incidence of diacapsular fracture of the mandibular condyle (DFMC) has increased in recent years. However, the specific modality of treatment which would provide maximum benefit and good results for adult patients of DFMC has been controversial. To evaluate and compare morphological changes of temporomandibular joint (TMJ) after open and closed treatments for DFMC, a sheep model of a type B DFMC was created by osteotomy. Eight sheep models of type B DFMC were randomly divided into 2 groups to receive closed treatment (Group 1) and open reduction and internal fixation (ORIF, Group 2), respectively, and morphological changes of TMJ were scored according to the radiological and anatomical criteria of scoring and compared between the 2 groups. Compared with Group 1 animals treated by the closed method, Group 2 animals treated with ORIF received significantly lower scores for morphological changes 12 weeks after treatment. We conclude that ORIF is more efficient than the closed functional treatment in restoring morphology of TMJ to treat type B DFMC.

A new hypothesis of mechanisms of traumatic ankylosis of temporomandibular joint.

Temporomandibular joint (TMJ) ankylosis is a disease that severely affects the human health. Although it is well known that trauma is the most common cause of TMJ ankylosis, the mechanisms by which the traumatic TMJ ankylosis develops are unclear. The existing hypothesis is not convincing in explaining the genesis of traumatic TMJ ankylosis. We make a hypothesis that the distraction osteogenesis (DO) of the lateral pterygoid muscle combining with the dislocated and damaged disc is an important factor in genesis of traumatic TMJ ankylosis. If this hypothesis is verified, it will be helpful for the prevention of traumatic TMJ ankylosis and change the principle of management of sagittal fracture of mandibular condyle (SFMC).