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Nevin Manimala Statistics

Value of information analysis for pandemic response: intensive care unit preparedness at the onset of COVID-19

BMC Health Serv Res. 2023 May 13;23(1):485. doi: 10.1186/s12913-023-09479-4.

ABSTRACT

BACKGROUND: During the early stages of the COVID-19 pandemic, there was considerable uncertainty surrounding epidemiological and clinical aspects of SARS-CoV-2. Governments around the world, starting from varying levels of pandemic preparedness, needed to make decisions about how to respond to SARS-CoV-2 with only limited information about transmission rates, disease severity and the likely effectiveness of public health interventions. In the face of such uncertainties, formal approaches to quantifying the value of information can help decision makers to prioritise research efforts.

METHODS: In this study we use Value of Information (VoI) analysis to quantify the likely benefit associated with reducing three key uncertainties present in the early stages of the COVID-19 pandemic: the basic reproduction number ([Formula: see text]), case severity (CS), and the relative infectiousness of children compared to adults (CI). The specific decision problem we consider is the optimal level of investment in intensive care unit (ICU) beds. Our analysis incorporates mathematical models of disease transmission and clinical pathways in order to estimate ICU demand and disease outcomes across a range of scenarios.

RESULTS: We found that VoI analysis enabled us to estimate the relative benefit of resolving different uncertainties about epidemiological and clinical aspects of SARS-CoV-2. Given the initial beliefs of an expert, obtaining more information about case severity had the highest parameter value of information, followed by the basic reproduction number [Formula: see text]. Resolving uncertainty about the relative infectiousness of children did not affect the decision about the number of ICU beds to be purchased for any COVID-19 outbreak scenarios defined by these three parameters.

CONCLUSION: For the scenarios where the value of information was high enough to justify monitoring, if CS and [Formula: see text] are known, management actions will not change when we learn about child infectiousness. VoI is an important tool for understanding the importance of each disease factor during outbreak preparedness and can help to prioritise the allocation of resources for relevant information.

PMID:37179300 | DOI:10.1186/s12913-023-09479-4

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Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls

J Transl Med. 2023 May 13;21(1):322. doi: 10.1186/s12967-023-04179-3.

ABSTRACT

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Cytokines are present in plasma and encapsulated in extracellular vesicles (EVs), but there have been only a few reports of EV characteristics and cargo in ME/CFS. Several small studies have previously described plasma proteins or protein pathways that are associated with ME/CFS.

METHODS: We prepared extracellular vesicles (EVs) from frozen plasma samples from a cohort of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) cases and controls with prior published plasma cytokine and plasma proteomics data. The cytokine content of the plasma-derived extracellular vesicles was determined by a multiplex assay and differences between patients and controls were assessed. We then performed multi-omic statistical analyses that considered not only this new data, but extensive clinical data describing the health of the subjects.

RESULTS: ME/CFS cases exhibited greater size and concentration of EVs in plasma. Assays of cytokine content in EVs revealed IL2 was significantly higher in cases. We observed numerous correlations among EV cytokines, among plasma cytokines, and among plasma proteins from mass spectrometry proteomics. Significant correlations between clinical data and protein levels suggest roles of particular proteins and pathways in the disease. For example, higher levels of the pro-inflammatory cytokines Granulocyte-Monocyte Colony-Stimulating Factor (CSF2) and Tumor Necrosis Factor (TNFα) were correlated with greater physical and fatigue symptoms in ME/CFS cases. Higher serine protease SERPINA5, which is involved in hemostasis, was correlated with higher SF-36 general health scores in ME/CFS. Machine learning classifiers were able to identify a list of 20 proteins that could discriminate between cases and controls, with XGBoost providing the best classification with 86.1% accuracy and a cross-validated AUROC value of 0.947. Random Forest distinguished cases from controls with 79.1% accuracy and an AUROC value of 0.891 using only 7 proteins.

CONCLUSIONS: These findings add to the substantial number of objective differences in biomolecules that have been identified in individuals with ME/CFS. The observed correlations of proteins important in immune responses and hemostasis with clinical data further implicates a disturbance of these functions in ME/CFS.

PMID:37179299 | DOI:10.1186/s12967-023-04179-3

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Nevin Manimala Statistics

Effect of orthodontic treatment on the periapical radiolucency of endodontically treated teeth: a CBCT analysis

BMC Oral Health. 2023 May 13;23(1):289. doi: 10.1186/s12903-023-02907-1.

ABSTRACT

BACKGROUND: This study aimed to evaluate periapical radiolucency of endodontically treated teeth before and after orthodontic treatment using cone-beam computed tomography (CBCT).

METHODS: Patients who underwent orthodontic treatment at Wonkwang University Daejeon Dental Hospital between January 2009 and June 2022 were included based on the following criteria: root canal treatment, and availability of CBCT images taken before and after orthodontic treatment with an interval of > 1 year between both scans. Patients with primary teeth or orthodontic tooth extractions were excluded. The size of the periapical radiolucency (SPR) of the endodontically treated tooth was evaluated using CBCT. Pre-orthodontic treatment CBCT images and the latest post-orthodontic treatment CBCT images were analyzed. The selected teeth were further categorized based on the orthodontic duration, CBCT interval, the patient sex and age, the tooth type and position (maxilla or mandible), and quality of root canal obturation. Statistical analyses were performed to evaluate changes in SPR using the paired t-test and multiple regression analysis.

RESULTS: In total, 115 teeth (37 anterior teeth, 22 premolars and 56 molars) from 61 patients (age, 14-54 years) were included, with 39 teeth from male patients and 76 teeth from female patients. The age was ranged between 14 and 54 years old, and mean age was 25.87 years old. The mean CBCT interval and orthodontic treatment period were 43.32 months and 36.84 months, respectively. Seventy-five teeth showed good obturation quality, 80 were not used as anchors during orthodontic treatment, and 71 were maxillary. The SPR size increased after orthodontic treatment for 56 teeth and decreased for 59 cases. The average change in SPR was -0.102 mm and the difference was not significant. Significant decrease of SPR were observed between female patients (p = 0.036) and maxillary teeth (p = 0.040).

CONCLUSION: Orthodontic treatment had no significant impact on the changes in the SPR in endodontically treated teeth in most categories. However, there was a significant difference among females and the maxillary teeth. In both categories, the size of radiolucency decreased significantly.

PMID:37179291 | DOI:10.1186/s12903-023-02907-1

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Nevin Manimala Statistics

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial

BMC Oral Health. 2023 May 13;23(1):288. doi: 10.1186/s12903-023-02966-4.

ABSTRACT

BACKGROUND: The aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT).

METHODS: Prior to RCT, the effect of trehalose (5-20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions.

RESULTS: In the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05).

CONCLUSIONS: The 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

PMID:37179287 | DOI:10.1186/s12903-023-02966-4

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Nevin Manimala Statistics

The significance of the microlymphangiogenesis, microangiogenesis, and combined detection of programmed cell death-1 protein (PD-1)/ki67 in gastric cancer tissues

J Cancer Res Clin Oncol. 2023 May 13. doi: 10.1007/s00432-023-04709-y. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the relationship between the microlymphangiogenesis, microangiogenesis, and combined detection of the programmed cell death-1 protein (PD-1)/ki67 in patients with gastric cancer as well as the disease prognosis.

METHODS: Immunohistochemistry was used to detect the microlymphatic density (MLD) and microvessel density (MVD) in the central and peripheral zones in 92 cases of gastric cancer, along with the number of PD-1- and ki67-positive tumor cells.

RESULTS: The central zone of the gastric cancer tissue contained fewer atretic cord-like lymphatic vessels than the peripheral zone, while the peripheral zone contained an increased number of lymphatic vessels compared with the central zone. In most cases, the lumen was also dilated. Compared with the MLD in the peripheral zone, the MLD in central zone was significantly decreased. Compared with the number of PD-1-positive cells in the peripheral zone, the number of PD-1-positive cells in the central zone was significantly decreased, and compared with the number of ki67-positive cells in the peripheral zone. The differences in the microlymphangiogenesis, microangiogenesis, and the number of PD-1- and ki67-positive cells among the different histological types were not statistically significant. The microlymphangiogenesis, microangiogenesis, and PD-1- and ki67-positive cells were significantly decreased in the gastric cancer tissues from the patients in stages T1 and T2 compared with the gastric cancer tissues from the patients in stages T3 and T4.

CONCLUSIONS: The detection of the MLD and MVD as well as the positive expression of PD-1 and ki67 in gastric cancer tissue are important reference indicators for judging the prognosis of gastric cancer.

PMID:37179266 | DOI:10.1007/s00432-023-04709-y

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Nevin Manimala Statistics

Statistical Considerations on the Use of RWD/RWE for Oncology Drug Approvals: Overview and Lessons Learned

Ther Innov Regul Sci. 2023 May 13. doi: 10.1007/s43441-023-00528-y. Online ahead of print.

ABSTRACT

Despite increasing utilization of real-world data (RWD)/real-world evidence (RWE) in regulatory submissions, their application to oncology drug approvals has seen limited success. Real-world data is most commonly summarized as a benchmark control for a single arm study or used to augment the concurrent control in a randomized clinical trial (RCT). While there has been substantial research on usage of RWD/RWE, our goal is to provide a comprehensive overview of their use in oncology drug approval submissions to inform future RWD/RWE study design. We will review examples of applications and summarize the strengths and weaknesses of each example identified by regulatory agencies. A few noteworthy case studies will be reviewed in detail. Operational aspects of RWD/RWE study design/analysis will be also discussed.

PMID:37179264 | DOI:10.1007/s43441-023-00528-y

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Nevin Manimala Statistics

Quantitative Analysis of Spatio-temporal Evolution Characteristics of Seasonal Average Maximum Temperature and Its Influence by Atmospheric Circulation in China from 1950 to 2019

Huan Jing Ke Xue. 2023 May 8;44(5):3003-3016. doi: 10.13227/j.hjkx.202205258.

ABSTRACT

Global warming and intensified human activities have led to regional climate instability with increasing frequency and the persistence of high-temperature climate events. Eco-environmental protection and socio-economic development have been faced with rigorous threats. Taking the monthly maximum temperatures from 1950 to 2019 as the basic data source, the spatial-temporal evolution characteristics of seasonal average maximum temperature (AMT) were discerned using the Mann-Kendall test and unary linear regression method in China from 1950 to 2019. Combined with linear correlation, partial linear correlation, and wavelet analysis, the correlation between seasonal AMT characteristics and atmospheric circulations was analyzed quantitatively. The results showed that:① the AMT in all seasons had a significant upward trend, with an increase of 1.21, 0.08, 1.81, and 0.25℃ in spring, summer, autumn, and winter, respectively. The abrupt change times of the AMT were concentrated in the 1990s to the early 21st century. ② In terms of spatial distribution, except for in summer, the average trend rates of AMT in other seasons increased gradually from south to north, although the increasing degrees were different. Among them, the AMT change rate in spring-winter was the fastest in northeast and northwest China. ③ There were complex correlations between the AMT of every season and atmospheric circulation factors, and the distribution of the interrelation energy varied significantly in different frequency domains. Specifically, the Pacific Decadal Oscillation had a significant negative correlation with AMT in summer. The North Atlantic Oscillation had an active effect on AMT changes in summer, autumn, and winter. The Arctic Oscillation had a significant positive driving effect on AMT in all seasons, and there were significant positive or negative influences on the short-or long-term changes of AMT in spring and summer due to the different EI Niño-Southern Oscillation years. These results could provide a theoretical basis and technical reference for China to formulate scientific and effective response plans of climate change.

PMID:37177972 | DOI:10.13227/j.hjkx.202205258

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Nevin Manimala Statistics

Research Progress on Spatial Differentiation and Influencing Factors of Soil Heavy Metals Based on Geographical Detector

Huan Jing Ke Xue. 2023 May 8;44(5):2799-2816. doi: 10.13227/j.hjkx.202205206.

ABSTRACT

The geographical detector is a new statistical method to detect spatial stratified heterogeneity and reveal the driving factors behind it. It can not only reveal the influence of a single factor on dependent variables but also evaluate the influence of two-factor interactions and does not need to consider linearity, while also avoiding the influence of multivariate collinearity. Without strong model assumptions, it solves the limitations of traditional methods in analyzing category variables. The research on the spatial differentiation of heavy metals in soil is increasingly widely used. This study collected 40 research reports on the spatial differentiation of soil heavy metals via geographical detector, combed the discrete methods of independent variables, research scale, dependent variables and types of independent variables, factor detection, exchange detection, risk detection, and ecological detection and put forward the problems that need to be clarified in the future application of this research. It is expected to provide support for the deep application of geo-detector in the field of spatial differentiation of soil heavy metals.

PMID:37177952 | DOI:10.13227/j.hjkx.202205206

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Nevin Manimala Statistics

Hydrochemical Characteristics and Control Factors of Groundwater in Shunping County, Hebei Province

Huan Jing Ke Xue. 2023 May 8;44(5):2601-2612. doi: 10.13227/j.hjkx.202205351.

ABSTRACT

In order to study the chemical characteristics and ion source of groundwater and further serve the scientific development and management of water resources in Shunping County. A total of 33 groups of karst water and 12 groups of pore water samples were collected systematically in Shunping County, and the hydrochemical types, composition characteristics, and main controlling factors of various types of groundwater were analyzed by using Gibbs diagram, ion ratio relation, and multivariate statistical analysis methods, and the contribution rates of various sources to groundwater solutes were evaluated. The results showed that the pore water and karst water in the study area were weakly alkaline, with TDS ranging from 245.89 to 430.00 mg·L-1 and 223.54 to 1347.80 mg·L-1, respectively. The anion components of groundwater were mainly HCO3 and Ca2+. Groundwater in the study area could be grouped into PW1 and PW2 pore water and KW1, KW2, and KW3 karst water. PW1 and KW1 were HCO3-Ca·Mg type, PW2 was HCO3·Cl-Ca·Mg type, KW2 was HCO3·NO3-Ca·Mg type, and KW3 was SO4-Ca·Mg type with high salinity. The weathering of carbonate rock mainly composed of dolomite and silicate rock mainly composed of albiar and potassium feldspar were the main material sources of groundwater, and their contributions to each water body were 39.69% to 66.13% and 11.87% to 58.38%. Sewage discharge and fertilizer use in human activities had significant effects on KW2 groundwater and PW1, PW2, and KW1 groundwater, respectively. In addition, the contribution rate of atmospheric precipitation to each water body ranged from 1.09% to 7.94% on average.

PMID:37177934 | DOI:10.13227/j.hjkx.202205351

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Nevin Manimala Statistics

A Cox Nomogram for Assessing Recurrence Free Survival in Hepatocellular Carcinoma Following Surgical Resection Using Dynamic Contrast-Enhanced MRI Radiomics

J Magn Reson Imaging. 2023 May 13. doi: 10.1002/jmri.28725. Online ahead of print.

ABSTRACT

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is difficult to predict and carries high mortality. This study utilized radiomic techniques with clinical examinations to assess recurrence in HCC.

PURPOSE: To develop a Cox nomogram to assess the risk of postoperative recurrence in HCC using radiomic features of three volumes of interest (VOIs) in preoperative dynamic contrast-enhanced MRI (DCE-MRI), along with clinical findings.

STUDY TYPE: Retrospective.

SUBJECTS: 249 patients with pathologically proven HCCs undergoing surgical resection at three institutions were selected.

FIELD STRENGTH/SEQUENCE: Fat saturated T2-weighted, Fat saturated T1-weighted, and DCE-MRI performed at 1.5 T and 3.0 T.

ASSESSMENT: Three VOIs were generated; the tumor VOI corresponds to the area from the tumor core to the outer perimeter of the tumor, the tumor +10 mm VOI represents the area from the tumor perimeter to 10 mm distal to the tumor in all directions, finally, the background liver parenchyma VOI represents the hepatic tissue outside the tumor. Three models were generated. The total radiomic model combined information from the three listed VOI’s above. The clinical-radiological model combines physical examination findings with imaging characteristics such as tumor size, margin features, and metastasis. The combined radiomic model includes features from both models listed above and showed the highest reliability for assessing 24-month survival for HCC.

STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) Cox regression, univariable, and multivariable Cox regression, Kmeans clustering, and Kaplan-Meier analysis. The discrimination performance of each model was quantified by the C-index. A P value <0.05 was considered statistically significant.

RESULTS: The combined radiomic model, which included features from the radiomic VOI’s and clinical imaging provided the highest performance (C-index: training cohort = 0.893, test cohort = 0.851, external cohort = 0.797) in assessing the survival of HCC.

CONCLUSION: The combined radiomic model provides superior ability to discern the possibility of recurrence-free survival in HCC over the total radiomic and the clinical-radiological models.

EVIDENCE LEVEL: 4.

TECHNICAL EFFICACY: Stage 2.

PMID:37177868 | DOI:10.1002/jmri.28725