Predicting quetiapine dose in patients with depression using machine learning techniques based on real-world evidence.

BACKGROUND: Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens. METHODS: The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model. RESULTS: Four predictors were selected from 38 variables by the univariate analysis (p < 0.05), including quetiapine TDM value, age, mean corpuscular hemoglobin concentration, and total bile acid. Ultimately, the XGBoost algorithm was used to create a prediction model for quetiapine dose that had the greatest predictive performance (accuracy = 0.69) out of nine models. In the testing cohort (62 cases), a total of 43 cases were correctly predicted of the quetiapine dose regimen. In dose subgroup analysis, AUROC for patients with daily dose of 100 mg, 200 mg, 300 mg and 400 mg were 0.99, 0.75, 0.93 and 0.86, respectively. CONCLUSIONS: In this work, machine learning techniques are used for the first time to estimate the dose of quetiapine for patients with depression, which is valuable for the clinical drug recommendations.

A machine learning model for predicting blood concentration of quetiapine in patients with schizophrenia and depression based on real-world data.

AIMS: This study aimed to establish a prediction model of quetiapine concentration in patients with schizophrenia and depression, based on real-world data via machine learning techniques to assist clinical regimen decisions. METHODS: A total of 650 cases of quetiapine therapeutic drug monitoring (TDM) data from 483 patients at the First Hospital of Hebei Medical University from 1 November 2019 to 31 August 2022 were included in the study. Univariate analysis and sequential forward selection (SFS) were implemented to screen the important variables influencing quetiapine TDM. After 10-fold cross validation, the algorithm with the optimal model performance was selected for predicting quetiapine TDM among nine models. SHapley Additive exPlanation was applied for model interpretation. RESULTS: Four variables (daily dose of quetiapine, type of mental illness, sex and CYP2D6 competitive substrates) were selected through univariate analysis (P < .05) and SFS to establish the models. The CatBoost algorithm with the best predictive ability (mean [SD] R2  = 0.63 ± 0.02, RMSE = 137.39 ± 10.56, MAE = 103.24 ± 7.23) was chosen for predicting quetiapine TDM among nine models. The mean (SD) accuracy of the predicted TDM within ±30% of the actual TDM was 49.46 ± 3.00%, and that of the recommended therapeutic range (200-750 ng mL-1 ) was 73.54 ± 8.3%. Compared with the PBPK model in a previous study, the CatBoost model shows slightly higher accuracy within ±100% of the actual value. CONCLUSIONS: This work is the first real-world study to predict the blood concentration of quetiapine in patients with schizophrenia and depression using artificial intelligent techniques, which is of significance and value for clinical medication guidance.

The distribution, sources and health risk of polycyclic aromatic hydrocarbons (PAHs) in sediments of Liujiang River Basin: A field study in typical karstic river.

The accumulation of PAHs in sediments of Liujiang River Basin were investigated to disclose the sources, input processes and toxicity risk of PAHs in a typical karstic river. The results revealed the concentrations of ∑15PAHs are ranging from 111.97 to 593.39 ng/g, most of which are centralized in upstream and midstream of Liujiang River. Positive Matrix Factorization identified PAHs are mainly from the mixed combustion of oil and coal, biomass combustion and oil products leaking. Redundancy analysis manifested mixed accumulation should be the main approach of PAHs that inputting sediment. The values of RQNCs and RQMPCs suggested the moderate contamination of PAHs. The higher HQ and ILCR indicated the ingestion of PAHs are the main way to impact public health, while children should be more susceptible to PAHs. The values of HQ and ILCR indicated the overall low non-carcinogenic risk of PAHs, but relatively high carcinogenic risk of PAHs.

The Size Screening Could Greatly Degrade the Health Risk of Fish Consuming Associated to Metals Pollution-An Investigation of Angling Fish in Guangzhou, China.

Fish size can heavily impact the bioaccumulation of metals, but it was rarely applied to screen out the fish with low health risk for consuming. Given the widespread metals contamination of angling fish, the angling fish collected from Guangzhou, China, were taken as an example in this study. The screening length and weight were detailed in accordance with the investigation of metals contamination among angling fish. Importantly, the feasibility of size screening on mitigating the health risk of angling fish was evaluated. The results revealed that the concentration of Cr and As were relatively high and beyond the maximum residue limit (MRL) in some fish. The mean pollution index (Pi) of As, Cr, and Pb were beyond 0.2, suggesting the widespread minor contamination. The total metal pollution index (MPI) manifested Oreochroms mossambcus was the most contaminated. The target hazard quotient (THQ) of Cr, As, and Hg were relatively higher, but the higher probability of THQ > 1 indicated the health risk should be dominantly from As. The highest TTHQ suggested the highest risk of Oreochroms mossambcus. Regression analysis determined the fish of THQ < 1 should be more likely centralized in the size that is beyond 13.7 cm and 45.0 g for adults and 19.8 cm and 127.9 g for children. Significantly reducing THQ among these screened fish confirmed their effect on the degrading health risk of metals; particularly, the children's THQ returned below 1. The commonly contaminated Oreochroms mossambcus was further excluded to remove the screened fish with THQ > 1; the further decrease in THQ confirmed that the exclusion of a contaminated species could improve the effect of size screening.

The Influence of the Reduction in Clay Sediments in the Level of Metals Bioavailability-An Investigation in Liujiang River Basin after Wet Season.

The seasonal elevation of metals' bioavailability can aggravate the threat of metal contamination in the aquatic environment. Nevertheless, their regulations have rarely been studied, particularly the connections between metals' transformation and environmental variations. Therefore, the catchment area of Liujiang River was taken as an example in this study, their seasonal variations in metals' bioavailability in sediments, especially during the wet season, was investigated to recover the processes associated with metals' speciations and multiple environmental factors. The results revealed that the concentration of metals in sediments were high overall in the wet season, but low in the dry season. The significantly reduced ratio of metals in non-residual forms was largely related to the overall reduction in metals in oxidizable and reducible forms after the wet season. However, the elevated BI indexes of most metals suggested their increased bioavailability in the dry season, which should be closely related to their corresponding elevations in carbonate-bound and exchangeable forms after the wet season. The variations in metals' bioavailability were primarily related to their predominance of exchangeable and carbonate-bound form. The higher correlation coefficients suggested the destabilization of the oxidizable form should be treated as a critical approach to the impact of metals' bioavailability after the wet season. In view of that, sediments' coarsening would pose the impacts on the destabilization of exogenous metals in sediments, the reduction in clay sediments should be responsible for the elevation of metals bioavailability after the wet season. Therefore, the monitoring of metals' bioavailability in sediments should be indispensable to prevent metal contamination from enlarging the scope of their threat to the aquatic environment of the river, especially after the wet season.

The Bioaccumulation and Health Risk Assessment of Metals among Two Most Consumed Species of Angling Fish (Cyprinus carpio and Pseudohemiculter dispar) in Liuzhou (China): Winter Should Be Treated as a Suitable Season for Fish Angling.

Wild fish caught by anglers were validated to be commonly polluted by metals, but their contamination status could be varied with changing seasons. To determine the seasonal variation in metal pollution and health risks in these fish, this study took Liuzhou City as an example to investigate the concentrations of eight metals in two dominant angling fishes (Cyprinus carpio and Pseudohemiculter dispar) collected, respectively, in winter and summer. The obtained results suggested the mean concentrations of metals in fish are overall lower in winter. Only Cr, Zn, and Cd in some fish were beyond the thresholds in summer. The significant correlations between fish length and weight and most metals suggested the biological dilution effect could exert its influence in winter. The similar distribution of metals in winter suggested that metal bioaccumulation should be manipulated by living habitats, while the inconsistent distribution of metals in summer may be related to the variation in feeding behavior. The metal pollution index (Pi) values were all below 0.2 in winter, which suggested no metal contamination in fish, but most fish were found to be mostly contaminated by Cr and Cd in summer, which was confirmed by their Pi > 0.2. The fish could be consumed freely in winter due to the total target hazard quotient (TTHQ) below 1, while the consumption of fish was not entirely safe in summer, particularly for children, due to TTHQ values that were generally beyond 1. Given the higher weekly recommended consumption of fish in winter, winter should be treated as a suitable season for fish angling.

The Accumulation and Transformation of Heavy Metals in Sediments of Liujiang River Basin in Southern China and Their Threatening on Water Security.

Heavy metal (HM) pollution in sediments is tightly related to the security of water quality in rivers, but the accumulation and conversion of HMs are poorly researched, so that a field study was conducted as an example in the Liujiang River Basin. Seven HMs were analyzed to determine between the overlying water and sediments. Moreover, the regulation of HMs speciation and environmental factors in their accumulation and conversion were identified. The obtained results suggested the HM concentrations in water are far below the primary standard of water quality, but in sediments, the contents of Cd and Zn are significantly higher than their corresponding baseline of soil. Only Cd and Pb are dominantly in non-residual form (carbonate-bound fraction and reducible fraction, respectively). The non-significant correlations suggested pH and Eh may be hard to influence HMs in water, while the significant correlations highlighted the regulations of Eh, organic matter and mean grain size on the accumulation of metals in sediments. The opposite correlations between EC, TDS, pH and Cd confirmed the emission of acid wastewater contributed to the accumulation of Cd in sediment. The conversion of metals between water and sediments were found to be significant only in specific forms of Cd, As, Cu, Zn and Pb, suggesting the conversion of HMs in sediments should be largely regulated by their specific forms. The very high risk disclosed by the higher values of Eri and RI are only found upstream, while the higher risk of Cd should be treated as a critical environmental threat.

The Variation of Heavy Metals Bioavailability in Sediments of Liujiang River Basin, SW China Associated to Their Speciations and Environmental Fluctuations, a Field Study in Typical Karstic River.

The bioavailability of heavy metals (HMs) in sediments is closely related to the security of the aquatic environment, but their impacts are poorly researched, particularly in karstic rivers. Therefore, Liujiang River Basin was taken as an example in this study. Seven HMs were analyzed to determine the bioavailability and speciations of HMs in sediments. Moreover, the impacts of environmental factors on HMs were identified. The obtained results suggested that HMs in the sediments are all within their permissible exposure limit (PEL), but Cd and Zn are significantly higher than the soil baseline. Most HMs were found to be in a residual fraction, while their exchangeable fraction was found to be in an extremely low ratio. HMs in bioavailable parts are significantly higher than in the exchangeable and carbonate-bound phases but lower than in the non-residual phase, which demonstrated that HM bioavailability is not confined to the exchangeable and carbonate-bound phases. The correlation coefficients commonly decreased with decreasing speciation ratios, which suggested that the overall bioavailability of metals should be determined by speciation ratios instead of speciations themselves. Noteworthily, most HMs in the residual form were found to be significantly correlated with their overall bioavailability, which highlighted the potential bioavailability of residual form. The non-correlations between pH, electrical conductivity (EC), total dissolved solids (TDS), and HM bioavailability suggested that HMs in the carbonate-bound phase are stable and unsusceptible to environmental variations, while the significant correlations between redox potential (Eh), turbidity, organic matter (OM), main grain size (Mz), and HM bioavailability suggested that HMs in the reducible and oxidizable forms are susceptible to environmental fluctuations. Therefore, the variation of HM bioavailability in karstic rivers is largely regulated by their reducible and oxidizable forms instead of their carbonate-bound form.

Effects of heavy metals speciations in sediments on their bioaccumulation in wild fish in rivers in Liuzhou-A typical karst catchment in southwest China.

Although fish are widely confirmed to be susceptible to heavy metals (HMs) contamination in sediments, this bioconversion haven't been detailed. This is especially the case in karst areas, where HMs are less stably retained in the sediments and are more bioavailable. Therefore, we surveyed representative karst rivers in Liuzhou, China, in order to study the relationship between the speciations of seven HMs in the sediments with their bioaccumulation in wild fish. The results showed that the HMs in sediments are all below their permissible exposure limit (PEL), but Cd and Zn are significantly higher than soil basline. Most HMs are in residual fraction, while their exchangeable fractions are present in extremely low proportions. The concentration of Zn, Cr and Cd in some fish are above their maximum recommended limit (MRL). The concentrations of most of the HMs in the fish are significantly correlated with the levels in the sediments and given the higher correlation coefficients for their carbonate-bound phase, this phase can be seen to play a critical role in HMs bioconversion. However, the presence of this phase in low proportions enables other phases, especially oxidizable form, to play a greater role in HMs bioaccumulation. Apart from Do, HMs in the fish samples are significantly correlated with multiple environmental factors, demonstrating environmental fluctuations can manipulate HMs bioconversion from sediments; however, their significance depend heavily on the proportion of particular species. HMs in reducible and oxidizable fraction are more important in regulating, rather than promoting, their bioconversion during environmental fluctuations. Fluctuations in EC, TDS and pH can increase the impacts of HMs in carbonate-bound fraction on their bioconversion. Given the higher background values of EC and TDS and lower pH values during the monsoon period, careful attention should be paid to the increased bioconversion of HMs in karst rivers during this season.

Health Risk Assessment of Metals (Cu, Pb, Zn, Cr, Cd, As, Hg, Se) in Angling Fish with Different Lengths Collected from Liuzhou, China.

Wild fish caught by anglers (WFAs) were confirmed to be usually contaminated with metals, and the contamination status is radically affected by the growth and length of the fish. To determine the contamination levels of metals and health risks in WFAs with different length ranges of fish, this study ascertained the concentration of eight metals, including Cu, Pb, Zn, Cr, Cd, As, Hg and Se, in 171 wild fishes collected from the watershed of Liujiang River. The assessment of metal pollution and health risks from the consumption of these fishes with seven length ranges were accomplished. The obtained results implied a relatively high concentration of Zn, Cr, and Cd up to 109.294 mg/kg, 4.226 mg/kg, and 0.196 mg/kg (wet weight), respectively, which exceed the corresponding Maximum Residue Limit (MRL). The negative correlation between Cu, Zn, Cr, and Cd was observed to be significant with fish length, signifying a possible occurrence of biological dilution on these metals. The WFAs were mostly contaminated with Cr and Cd irrespective of the length ranges of fish, which were denoted by the average pollution index (Pi) of Cr and Cd and were commonly found to be beyond 0.2. Based on the results of health risk assessment analysis, most of the target hazard quotient (THQ) values of Cr were below 1, implying that the consumption of wild fish for adults has insignificant health risk. For children, the total target hazard quotient (TTHQ) values of beyond 1 were found in fishes with the length range of <25 cm, particularly a TTHQ value 1.627 in the range of 10-15 cm, indicating that children are being prone to serious health risks owing to the consumption of WFAs. The weekly recommended consumption of WFAs with the length range of 10-15 cm for adults and children was 0.298 kg/week and 0.149 kg/week, respectively. These are substantially lower than the current rate of fish consumption (0.42 kg/week), and therefore, the wild fish with the length range of 10-15 cm should be avoided for consumption.

Spatial distribution of heavy metals and their potential sources in the soil of Yellow River Delta: a traditional oil field in China.

In this study, soil samples were collected from different layers throughout the whole Yellow River Delta (YERD), in north China. The total concentration of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), lead (Pb) and zinc (Zn) was determined to demonstrate their spatial distribution and pollution status in different layers of soils throughout the whole YERD. The obtained results suggested a relatively low contamination of heavy metals as observed through the evaluation of CF and RI. The potential ecological risk of Hg is not so severe. Also, the maximum potential threat could be noted only from Cd instead of Hg based on the widespread degree of pollution, which breaks traditional concept that oil production escalates mercury in the soil. The obtained value of EF proves a higher enrichment of heavy metals in the surface soil than in the layer of deep soil induced by human activities. Human activities only slightly elevate As, Cd and Pb. As has the strongest ability downward to lower layer, followed by Cd and Pb in YERD. The source of heavy metals predominantly stems from natural deposits, and their concentrations are controlled by the nature of their association with the mineral. Overall, it shows that the petroleum industry instead of agriculture could be treated as an important source to bring anthropogenic heavy metals in the soils. The human influence only elevated the concentration of heavy metals in the soil of the areas corresponding to the intensive production of oil. In this study some of the measures have also been proposed to avoid and control soil pollution as well as the health risk caused by heavy metals.

Correction to: Spatial distribution of heavy metals and their potential sources in the soil of Yellow River Delta: a traditional oil field in China.

In the original publication of the article, the sixth author name "Zhouqing Xie" has been misspelt. The correct name is given in this correction. The original version of this article was revised.

Analysis and health risk assessment of toxic and essential elements of the wild fish caught by anglers in Liuzhou as a large industrial city of China.

Most wild fish caught by anglers (WFAs) are likely to be contaminated by toxic metals, particularly the fish collected from the waterways in urban and suburban areas; hence, the determination of health risk caused by WFAs consumption associated with toxic metals is vital. Therefore, Liuzhou, one of the largest industrial cities in China, was considered as an example city in this study. Eight toxic elements were analysed to uncover the pollution status and consumption safety of WFAs. Moreover, the suitable angling waterways were identified in the urban and suburban areas. The obtained results suggested relatively high concentrations of Zn, Cr and Cd, which were also found to be beyond corresponding Maximum Residue Limit. Among all analysed elements, only the mean pollution indices of Cr and Cd were observed to be beyond 0.2, revealing that the observed WFAs were generally contaminated by these metals. However, the potential health risk of WFAs can be predominately attributed to Cr, confirmed by the significantly higher Target hazard quotients (THQ). For adults, all the THQ values were below 1, indicating no significant health risk being associated with WFAs consumption in the case of adults. On the contrary, all the THQ values for Children were beyond 1, suggesting children being susceptible to great health risks due to WFAs consumption. Furthermore, the weekly recommended consumption of WFAs in urban area is remarkably lower than the current rate of fish consumption observed among urban residents; therefore, the waterways in urban areas can be evaded for fish angling.