Category: Statistics

Ther Innov Regul Sci. 2022 Jan 30. doi: 10.1007/s43441-021-00368-8. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, population pharmacokinetics (PK) has been widely used in neonatal pharmacology. However, the sample size selection for neonatal PK studies has been highly variable and without clear consensus, especially for drugs with large individual variability. Therefore, this study’s objective was to investigate the optimal sample size for use in neonatal PK studies.

METHODS: A comprehensive and reliable population PK model (1631 neonates) of vancomycin was selected as a reference model. The original sparse PK dataset was divided into several sub-datasets according to different sample sizes. NONMEM was used for sub-datasets PK analysis. Statistical powers were calculated to evaluate different sample sizes (> 80% was expected).

RESULTS: During population clearance estimations, the average power was 40%, 85%, 100%, and 100% for sample sizes of 10, 25, 50, and 100 neonates, respectively. And the frequency of model-estimated median clearance values within ± 10% (relative errors) of target value (0.057 L/h) were 75.0%, 68.8%, 57.8%, and 35.0%, respectively. Regarding age sub-groups (postmenstrual age (PMA) < or ≥ 37 weeks) clearance estimation, a sample size of 50 was better to complete the assessment of the neonatal age sub-group even in some cases of unbalanced age distribution.

CONCLUSION: A sample size of 25 neonates provided a consistent estimation of the overall population (PMA: 23.3-52.4 weeks) clearance for a drug with high individual variability using a sparse PK sampling design. A sample size of 50 was recommended to complete neonatal age sub-group assessments.

PMID:35094368 | DOI:10.1007/s43441-021-00368-8

Daru. 2022 Jan 30. doi: 10.1007/s40199-021-00423-7. Online ahead of print.

ABSTRACT

OBJECTIVES: There are a multitude of different modelling techniques that have been used for inhaled drugs. The main objective of this review was to conduct an exhaustive survey of published mathematical models in the area of asthma and chronic obstructive pulmonary disease (COPD) for inhalation drugs. Additionally, this review will attempt to assess the applicability of these models to assess bioequivalence (BE) of orally inhaled products (OIPs).

EVIDENCE ACQUISITION: PubMed, Science Direct, Web of Science, and Scopus databases were searched from 1996 to 2020, to find studies that described mathematical models used for inhaled drugs in asthma/COPD.

RESULTS: 50 articles were finally included in this systematic review. This research identified 22 articles on in silico aerosol deposition models, 20 articles related to population pharmacokinetics and 8 articles on physiologically based pharmacokinetic modelling (PBPK) modelling for inhaled drugs in asthma/COPD. Among all the aerosol deposition models, computational fluid dynamics (CFD) simulations are more likely to predict regional aerosol deposition pattern in human respiratory tracts. Across the population PK articles, body weight, gender, age and smoking status were the most common covariates that were found to be significant. Further, limited published PBPK models reported approximately 29 parameters relevant for absorption and distribution of inhaled drugs. The strengths and weaknesses of each modelling technique has also been reviewed.

CONCLUSION: Overall, while there are different modelling techniques that have been used for inhaled drugs in asthma and COPD, there is very limited application of these models for assessment of bioequivalence of OIPs. This review also provides a ready reference of various parameters that have been considered in various models which will aid in evaluation if one model or hybrid in silico models need to be considered when assessing bioequivalence of OIPs.

PMID:35094370 | DOI:10.1007/s40199-021-00423-7

Updates Surg. 2022 Jan 30. doi: 10.1007/s13304-021-01201-5. Online ahead of print.

ABSTRACT

Metabolic surgery has become a powerful treatment for obese type 2 diabetes (T2DM). Experts have been devoting to the research of metabolic surgery in the treatment of T2DM. The debate continues, and there is no comprehensive statistical and intuitive analysis for it. To explore the current research status, the latest hotspots and the changing trend in this field, we conducted a bibliometric analysis. This paper made a bibliometric analysis based on the data source from Science Core Collection Network (WoSCC). Vosviewer v.1.6.10 software is used to construct a knowledge map. From 2011 to 2020, 1424 peer-reviewed papers on metabolic surgery for T2DM were retrieved. The United States contributed the most publications and gained global impact with the most citations. Obesity Surgery was the most prolific journal in this field. Prof. Schauer Philip R., Prof. Buchwald H. and Prof. Sjostrom L. were the most renowned experts in this aspect. The top cited references discussed the status of metabolic surgery for the treatment of T2DM worldwide and the importance of regular evaluation. The extracted keywords mainly formed three clusters: (1) research on the selection of different metabolic surgery methods; (2) possible mechanisms; (3) improvement of T2DM complications by metabolic surgery. Our study makes a comprehensive and objective analysis of metabolic surgery in obese patients with T2DM, providing valuable information for further clinical application and related scientific research. Researchers can quickly locate research hotspots in a large number of relevant literature.

PMID:35094308 | DOI:10.1007/s13304-021-01201-5

Endocrine. 2022 Jan 30. doi: 10.1007/s12020-021-02975-9. Online ahead of print.

ABSTRACT

PURPOSE: Achieving preoperative euthyroidism in patients with hyperthyroidism for whom antithyroid drugs (ATDs) cannot be used for treatment is a serious clinical problem. We aimed to evaluate the effectiveness of therapeutic plasma exchange (TPE) in hyperthyroid patients scheduled for surgery and predictive factors for a high number of TPE sessions.

METHODS: We retrospectively analyzed the data of 21 patients with hyperthyroidism who were treated with TPE for preoperative euthyroidism in our institution. Pre- and post-TPE thyroid function tests were compared to assess efficacy. Binary logistic regression analysis was applied to determine predictors of patients requiring a high number of TPE sessions.

RESULTS: All patients (20 patients with Graves’ disease and 1 patient with toxic multinodular goiter; 12 women and 9 men; mean age 35.71 ± 12.38 years) had severe hyperthyroidism before TPE. The changes before and after TPE in fT3, fT4, and TSH levels were statistically significant (p < 0.001, p < 0.001, p = 0.002, respectively). The median number of TPE sessions was 8 (range: 1-24). Levels of fT3 before TPE were significantly higher in patients for whom higher numbers of TPE sessions were required (≥8) (OR: 1.427, 95% CI: 1.038-1.961, p = 0.028). Receiver operating characteristic curve analysis revealed an optimum cut-off value of 12.8 pg/ml for fT3 before TPE (91% sensitivity, 80% specificity, area under the curve: 0.927).

CONCLUSION: TPE should be considered as an effective alternative treatment option that can be used to rapidly achieve euthyroidism before surgery when ATDs cannot be used. Pre-TPE fT3 levels of >12.8 pg/ml may be an independent factor predicting the need for higher numbers of TPE sessions (≥8).

PMID:35094312 | DOI:10.1007/s12020-021-02975-9

Dermatol Ther (Heidelb). 2022 Jan 29. doi: 10.1007/s13555-022-00682-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Notwithstanding their numerous advantages, biological treatments have many limitations when treating patients with psoriasis (PsO) and hepatitis B (HB). Clinicians need to pay careful attention to the issue of hepatitis B virus (HBV) reactivation.

METHODS: In accordance with the PRISMA guidelines, we systematically searched Pubmed, Scopus, Embase, Cochrane Library, and Web of Science databases for observational studies on the topic of HBV reactivation among patients with PsO and HB treated with biologics. The random-effects model was used to pool the reactivation rate by the Freeman-Tukey double arcsine transformation method. We selected Fisher’s exact test to compare multiple rates. To determine the sources of heterogeneity, sensitivity analysis and meta-regression were performed.

RESULTS: Ten studies with a total of 238 subjects that met the inclusion criteria were included. The pooled reactivation rate was 1.8% [95% confidence interval (CI) 0.0-5.6%] in patients with PsO and HB. Among them, the viral reactivation rates of HBsAg-positive and HBsAg-negative patients were 4.1% (95% CI 0.0-17.9%) and 0.2% (95% CI 0.0-2.8%). The difference between HBsAg-positive and HBsAg-negative patients was statistically significant (p = 0.002). The viral reactivation rate of individuals who needed antiviral prophylaxis but did not receive it was 26.6% (95% CI 5.8-53.5%), while it decreased to 0.0% (95% CI 0.0-6.6%) after accepting antiviral treatment. The two-sided Fisher’s test exact values between different durations of biological therapy showed no statistical significance (p = 0.104).

CONCLUSIONS: Without antiviral prophylaxis, HBsAg-positive patients with psoriasis are at high risk of virus reactivation when treated with biological agents. Early and sufficient antiviral prophylaxis will effectively reduce the risk of HBV reactivation and serious complications in HBsAg-positive patients. Prolonging the duration of biological treatment will not increase the risk of reactivation.

PMID:35094295 | DOI:10.1007/s13555-022-00682-5

Environ Sci Pollut Res Int. 2022 Jan 30. doi: 10.1007/s11356-021-18210-x. Online ahead of print.

ABSTRACT

Climate change continues to pose a threat to the agricultural sectors worldwide, jeopardizing food and nutritional security, which is a critical component of the sustainable development agenda. Consequently, this study attempts to examine the impact of climatic variables (CO₂ emissions, energy resources, rainfall, temperature, fossil fuel consumption, and humidity) on agricultural production of rice, cereals, vegetables, coffee, and agriculture value added (as a percentage of GDP) in the Malaysian context. To this end, this study applied a generalized method of moments (GMM) estimator on the data obtained from the metrological station Malaysia, Department of Statistics Malaysia and World Development Indicators (WDI) spanning the period 1985-2016. The results revealed that temperature and energy consumption negatively and significantly affect rice and vegetable production, while the negative effect of rainfall, temperature, fossil fuel consumption, and humidity on cereal production is insignificant. The results also confirmed that CO₂ emissions have a negative and significant impact on coffee production. Likewise, temperature, energy consumption, and fossil fuel consumption exhibit a negative and significant influence on agriculture value added. These observations evidenced the adverse effect of climate change on various agricultural products in Malaysia. Therefore, in order to ensure robust and sustainable agricultural output in Malaysia, policymakers as well as environmentalists should work together to formulate appropriate adaptation strategies.

PMID:35094275 | DOI:10.1007/s11356-021-18210-x

Genes Genomics. 2022 Jan 30. doi: 10.1007/s13258-021-01209-6. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes (T2DM) susceptibility varies among different populations and is affected by gene single nucleotide polymorphism (SNP). Insulin-like growth factor (IGF)-1 gene, which has many SNP loci, is involved in T2DM pathogenesis. However, the relationship of IGF-1 gene polymorphism with T2DM in Uyghur population is less studied.

OBJECTIVE: To investigate the relationship between T2DM susceptibility and polymorphism of IGF-1 gene in Uyghur population of Xinjiang, China.

METHODS: This study enrolled 220 cases (122 males (55.46%) and 98 females (44.54%); mean age of 53.40 ± 10.94 years) of T2DM patients (T2DM group) and 229 (124 males (54.15%) and 105 females (45.85%); mean age of 51.64 ± 10.48 years) healthy controls (control group). Biochemical indexes were determined. IGF-1 gene polymorphism was analyzed by SNP genotyping.

RESULTS: The levels of TG, HDL, LDL, BUN, and Cr were statistically significant between the T2DM group and the control group. In terms of IGF-1 polymorphism, T2DM group had higher frequency of AA genotype (OR = 2.40, 95% CI = 1.19-4.84) and allele A (OR = 1.55, 95% CI = 1.17-2.06) of rs35767 loci, suggesting that rs35767 is related to the occurrence of T2DM. A total of 5 gene interaction models was obtained through analyzing the interaction of 5 SNP loci with the GMDR method. Among them, the two-factor model that included rs35767 locus and rs5742694 locus had statistical difference with a large cross-validation consistency (10/10). The combination of GG/CC, GA/AA, AA/AA, and AA/AC genotype was in high-risk group, whereas the combination of GG/AA, GG/AC, GA/AC and GA/CC genotype was in the low-risk group. The risk of T2DM in the high-risk group was 2.165 times than that of the low-risk group (OR = 2.165, 95% CI = 1.478-3.171).

CONCLUSION: TG, HDL, LDL, BUN, and Cr are influencing factors of T2DM in Uyghur population. The rs35767 locus of IGF-1 gene may be associated with T2DM in Uyghur population. The high-risk group composing of rs35767 locus and rs5742694 locus has a higher risk of T2DM.

PMID:35094288 | DOI:10.1007/s13258-021-01209-6

Environ Sci Pollut Res Int. 2022 Jan 30. doi: 10.1007/s11356-021-18353-x. Online ahead of print.

ABSTRACT

China has witnessed significant growth in trade through vide range trade liberalization strategies and urbanization has also been entered in advanced stage. Based on these dynamics, how much energy consumption of both renewable and none renewable account for energy consumption in whole system is a point of higher attention for the researchers. To understand this salient emerging debatable concern, we investigate the impact of trade openness and urbanization effect on renewable and non-renewable energy consumption in China for the period 1990-2018. We apply the quantile regression technique for the analysis; our results show that trade significantly increases the non-renewable energy consumption in all quintiles while partially increasing renewable energy consumption. This shows that trade activities in production and export commodities heavily rely on non-renewable energy inputs instead of renewable energy inputs. Urbanization affects non-renewable energy consumption only in three quintiles, while its effect is insignificant in most of the quintiles. Similarly, urbanization does not affect renewable energy consumption as in almost all quantiles the coefficients are statistically insignificant. This implies that urbanization is one of the determinants of energy consumption in China. The empirical findings of this study suggest some policy recommendations; first, the government needs to implement certain regulations while expanding trade to minimize the negative effect of non-renewable energy consumption; besides government should provide incentives to industrial units and traders for using renewable energy which may help to attain long term sustainable development goals. The government should also put certain limitations on population moving from rural to urban destinations.

PMID:35094269 | DOI:10.1007/s11356-021-18353-x

Environ Sci Pollut Res Int. 2022 Jan 30. doi: 10.1007/s11356-021-18173-z. Online ahead of print.

ABSTRACT

The characterization of the day-to-night changes of the atmospheric particle chemical and optical properties in autumn-winter (AW) and spring-summer (SS) is the main goal of this study to contribute to the characterization and understanding of the particulate matter (PM) impact on the environment and climate at one of the most vulnerable areas of the planet to climate change. To this end, PM10 and PM2.5 samples from 14 January 2016 to 5 January 2017 have been collected in Lecce, a coastal site of South-Eastern Italy (40.33°N, 18.11°E), and day-to-night changes of mass concentrations of both fine (PM2.5) and coarse (PM10-PM2.5) particles and corresponding chemical species have been assessed both in AW and in SS. The statistical analysis of local meteorological parameters and their correlations with PM2.5 and chemical species mass concentrations have indicated that the day-to-night changes of temperature (T) and wind speed (WS) likely affected the day-to-night changes of mass concentrations, because of the T and WS impact on the atmospheric turbulence and air particle dispersion. The daily evolution of the anthropogenic activities and the planetary-boundary-layer height likely contributed to the day-to-night changes of the particle chemical composition. The stagnant atmospheric conditions prevailing in SS all over the Mediterranean basin, which favoured the mixing and the accumulation of atmospheric particles from different pollution sources, likely contributed to the changes of the relationships between chemical species and meteorological parameters from AW to SS at daytime and nighttime. The analysis of the aerosol scattering coefficient, scattering Ångström exponent, and scattering Ångström exponent difference, retrieved from nephelometer measurements co-located in space and time with the PM samplings, has allowed characterizing the day-to-night change of the aerosol optical properties. The relationships between the particle chemical and optical properties allowed a good understanding of their changes both in AW and in SS.

PMID:35094266 | DOI:10.1007/s11356-021-18173-z

Environ Sci Pollut Res Int. 2022 Jan 30. doi: 10.1007/s11356-022-18908-6. Online ahead of print.

ABSTRACT

Considering the current global goal of carbon neutrality, the relationship between cultivated land intensive use (CLIU) and carbon emission efficiency (CEE) should be explored to address the global climate crisis and move toward a low-carbon future. However, previous work in this has been conducted at provincial/regional scales and few have identified the spatial correlation between CLIU and CEE at the scale of large river basins. Therefore, this study explored the spatiotemporal characteristics of CLIU, cultivated land carbon emissions (CLCE), and CEE, as well as the spatial correlation between CLIU and CEE in the Yellow River Basin (YRB), China. A comprehensive evaluation model, the Intergovernmental Panel on Climate Change (IPCC) coefficient methodology, existing data envelopment analysis model, and bivariate spatial autocorrelation models were used to analyze statistical data from 2005 to 2017. We found that the overall CLIU and CLCE values in the YRB exhibited a continuous increase; the average carbon emission total efficiency and carbon emission scale efficiency first decreased and then increased, and the average carbon emission pure technical efficiency gradually decreased. Areas of high CLCE were concentrated in eastern areas of the YRB, whereas those of high CLIU, carbon emission total efficiency, carbon emission scale efficiency, and carbon emission pure technical efficiency predominantly appeared in the eastern areas, followed by central and western areas of the YRB. Spatial analysis revealed a significant spatial dependence of CLIU on CEE. From a global perspective, the spatial correlations between CLIU and CEE changed from positive to negative with time. Moreover, the aggregation degree between CLIU and CEE gradually decreases with time, while the dispersion degree increases with time, and the spatial correlation gradually weakens. The local spatial autocorrelation further demonstrates that the number of high-low and low-high clusters between CLIU and CEE gradually increases over time, while the number of high-high and low-low clusters gradually decreased over time. Collectively, these findings can help policymakers formulate feasible low-carbon and efficient CLIU policies to promote win-win cooperation among regions.

PMID:35094255 | DOI:10.1007/s11356-022-18908-6