Category: Statistics

Accid Anal Prev. 2021 Nov 29;165:106507. doi: 10.1016/j.aap.2021.106507. Online ahead of print.

ABSTRACT

Numerous evaluation studies have been conducted on a variety of road safety measures. However, the issue of treatment heterogeneity, defined as the variation in treatment effects, has rarely been investigated before. This paper contributes to the literature by introducing generalized random forests (GRF) for estimation of heterogeneous treatment effects (HTEs) in road safety analysis. GRF has high functional flexibility and is able to search for complex treatment heterogeneity. We first perform a series of simulation experiments to compare GRF with three causal methods that have been used in road safety studies, i.e., outcome regression method, propensity score method, and doubly robust estimation method. The simulation results suggest that GRF is superior to these three methods in terms of model specification, especially with the existence of nonlinearity and nonadditivity. On the other hand, a large dataset is required for accurate GRF estimation. Then we conduct a case study on the UK’s speed camera program. Our results indicate significant reductions in the number of road accidents at speed camera sites. And the heterogeneity in treatment effects is found to be statistically significant. We further consider the associations between the baseline accident records, traffic volume, local socio-economic characteristics, and the safety effects of speed cameras. In general, the effect of speed cameras is larger at the sites with more baseline accident records, higher traffic volume, and in more densely-populated and deprived areas. Several policy suggestions are provided based on these findings. The evaluation of HTEs likely offers more comprehensive information to local authorities and policy makers, and improves the performance of speed camera programs. Moreover, GRF can be a promising approach for revealing treatment effect heterogeneity in road safety analysis.

PMID:34856506 | DOI:10.1016/j.aap.2021.106507

Comput Biol Med. 2021 Nov 26;140:105072. doi: 10.1016/j.compbiomed.2021.105072. Online ahead of print.

ABSTRACT

BACKGROUND: Carotid endarterectomy (CEA) remains the first-line treatment option of symptomatic and asymptomatic carotid stenosis, while stenting (CAS) is reserved for selected patients at high surgical risk. Here, we compare the vascular remodeling process in CEA- and CAS-treated patients with respect to morphological and hemodynamic features, because of their possible engagement in carotid atherosclerosis.

METHODS: Twelve (12) patients were included, half with patched CEA and half with CAS. Pre- and post-operative 3D image-based models of the carotid bifurcation were anatomically characterized in terms of flare, tortuosity, and curvature. Individual computational fluid dynamics simulations allowed to quantify the postoperative hemodynamic milieu in terms of (1) wall shear stress and (2) helical flow.

RESULTS: Carotid flare increased in all cases, but a more marked increase emerged after CEA compared to CAS. Tortuosity and curvature increased after CEA but decreased after CAS. CEA patients presented with significantly higher postoperative tortuosity than CAS patients. CEA was associated with a worse (non-statistically significant) score in all flow disturbance indicators vs. CAS.

CONCLUSION: The increased flare and tortuosity of the carotid bifurcation after CEA vs. CAS is a marked difference in the vascular remodeling process between the two modalities. CAS seems to induce a less pro-restenosis hemodynamic environment compared to CEA. The emerged differences stimulate further analysis on a larger cohort with long-term outcomes, to shed light on the clinical impact of the observations.

PMID:34856465 | DOI:10.1016/j.compbiomed.2021.105072

Ideggyogy Sz. 2021 Nov 30;74(11-12):389-396. doi: 10.18071/isz.74.0389.

ABSTRACT

BACKGROUND AND PURPOSE: We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients.

METHODS: This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine.

RESULTS: Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05-1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27-3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16-0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding.

CONCLUSION: Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

PMID:34856085 | DOI:10.18071/isz.74.0389

Ideggyogy Sz. 2021 Nov 30;74(11-12):397-407. doi: 10.18071/isz.74.0397.

ABSTRACT

BACKGROUND AND PURPOSE: Conventional parameters used in electrodiagnosis of ulnar neuropathy at elbow (UNE) are: (i) absolute across-elbow ulnar nerve motor conduction velocity (MCV), (ii) reduction rate of composed muscle action potential (CMAP) amplitude from above to below elbow stimulation, and (iii) MCV difference between forearm and across-elbow segment. We aimed to search the diagnostic accuracy values of these parameters on UNE, and their correlations with axonal dysfunction of ulnar nerve fibers.

METHODS: Arms with clinical signs of UNE and two-fold healthy controls were included. We detected the best cut off points of the measured parameters and their possible combinations. Their diagnostic accuracy values and correlations with parameters reflecting the axonal functions were analyzed, statistically.

RESULTS: Totally, 118 arms with UNE and 236 controls were included. Absolute across-elbow MCV yielded a higher accuracy than MCV difference and reduction rate of CMAP amplitude (p = 0.010 and p˂0.001, respectively). Besides, combining it with other parameters did not increase the diagnostic yield. Correlation analyses revealed that the only parameter having positive linear correlations with sensory nerve action potential amplitudes both in the control and the disease groups is the absolute across-elbow MCV. The absolute across-elbow MCVs have also positive linear correlation with CMAP amplitudes in disease group.

CONCLUSION: The absolute across-elbow MCV is the most valuable conventional parameter for the electrodiagnosis of UNE. It is also the most correlated parameter with the electrodiagnostic parameters reflecting the axonal functions of the ulnar nerve fibers.

PMID:34856084 | DOI:10.18071/isz.74.0397

Endocrinol Diabetes Metab. 2021 Dec 1:e00316. doi: 10.1002/edm2.316. Online ahead of print.

ABSTRACT

INTRODUCTION: Longitudinal data on management and progression of type 2 diabetes mellitus (T2DM) in India are scarce. LANDMARC (CTRI/2017/05/008452), first-of-its-kind, pan-India, prospective, observational study aimed to evaluate real-world patterns and management of T2DM over 3 years.

METHODS: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrolment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. The first-year trends for glycaemic control, therapy and diabetic complications, including those from metropolitan and non-metropolitan cities are reported here.

RESULTS: Of 6236 enrolled participants, 5654 completed 1 year in the study. Although the overall mean glycated haemoglobin (HbA1c) improved by 0.5% (baseline: 8.1%) at 1 year, only 20% of the participants achieved HbA1c <7%. Participants from metropolitan and non- metropolitan cities showed similar decrease in glycaemic levels (mean change in HbA1c: -0.5% vs. -0.5%; p = .8613). Among diabetic complications, neuropathy was the predominant complication (815/6236, 13.1% participants). Microvascular complications (neuropathy, nephropathy and retinopathy) were significantly (p < .0001) higher in non-metropolitan than metropolitan cities. Hypertension (2623/6236, 78.2%) and dyslipidaemia (1696/6236, 50.6%) continued to be the most commonly reported cardiovascular risks at 1 year. After 1 year, majority of the participants were taking only oral anti-diabetic drugs (OADs) (baseline: 4642/6236 [74.4%]; 1 year: 4045/6013 [67.3%]), while the proportion of those taking insulin along with OADs increased (baseline: 1498/6236 [24.0%] vs. 1 year: 1844/6013 [30.7%]). Biguanides and sulfonylureas were the most used OADs. The highest increase in use was seen for dipeptidyl peptidase-IV inhibitors (baseline: 3047/6236 [48.9%]; 1 year: 3529/6013 [58.7%]). Improvement in all glycaemic parameters was significantly (p < .0001) higher in the insulin vs. the insulin-naïve subgroups; in the insulin-naïve subgroup, no statistical difference was noted in those who received >3 vs. ≤3 OADs.

CONCLUSIONS: First-year trends of the LANDMARC study offer insights into real-world disease progression, suggesting the need for controlling risk factors and timely treatment intensification in people with T2DM.

PMID:34856077 | DOI:10.1002/edm2.316

Mol Oncol. 2021 Dec 2. doi: 10.1002/1878-0261.13148. Online ahead of print.

ABSTRACT

Nutritional intervention is becoming more prevalent as adjuvant therapy for many cancers in view of the tumor dependence on external sources for some nutrients. However, little is known about the mechanisms that render cancer cells dependent on certain nutrients from the microenvironment. Herein, we report the dependence of glioma cells on exogenous cysteine/cystine, despite this amino acid being nonessential. Using several ¹³ C-tracers and analysis of cystathionine synthase and cystathioninase levels, we revealed that glioma cells were not able to support GSH synthesis through the transsulfuration pathway, which allows methionine to be converted to cysteine in cysteine/cystine deprived conditions. Therefore, we explored the nutritional deprivation in a mouse model of glioma. Animals subjected to a cysteine/cystine-free diet survived longer, although this increase did not attain statistical significance, with concomitant reductions in plasma glutathione and cysteine levels. At the end point, however, tumors displayed the ability to synthesize glutathione, although higher levels of oxidative stress were detected. We observed a compensation from the nutritional intervention revealed as the recovery of cysteine-related metabolites levels in plasma. Our study highlights a time window where cysteine deprivation can be exploited for additional therapeutic strategies.

PMID:34856072 | DOI:10.1002/1878-0261.13148

Chemphyschem. 2021 Dec 1. doi: 10.1002/cphc.202100765. Online ahead of print.

ABSTRACT

We propose here a theoretical model for the influence of confinement on biomolecular binding at the single-molecule scale at equilibrium, based on the change of the number of microstates (localization and orientation) upon reaction. Three cases studies are discussed: DNA sequences shorter and longer than the single strain DNA Kuhn length and spherical proteins, confined into a spherical container (liposome, droplet…). The results show that this influence is highly dependent on the molecular structure and significant for large molecules (relative to container size).

PMID:34856050 | DOI:10.1002/cphc.202100765

J Hepatobiliary Pancreat Sci. 2021 Dec 2. doi: 10.1002/jhbp.1089. Online ahead of print.

ABSTRACT

BACKGROUND: There is a strong interaction between hepatic hemodynamics and perfusion in the splanchnic system. However, little is known about differences in perfusion in different splanchnic compartments and their changes after hepatectomy.

METHODS: Perfusion in various splanchnic compartments (i.e. stomach, small intestine, right and left colon, liver) was assessed pre- and post-hepatectomy by intraoperative laser Doppler flowmetry. Differences of splanchnic perfusion between compartments were evaluated by ANOVA, and risk factors of postoperative complications (graded by the comprehensive complication index (CCI)) were analyzed by univariate and multivariate analyses. A prediction model of postoperative complications was developed.

RESULTS: A total of 50 and 29 patients with major and minor hepatectomy were enrolled. Splanchnic perfusion at baseline varied significantly across different splanchnic compartments with highest values in the small bowel and right colon (P < 0.001). Major hepatectomy induced a significant perfusion decrease in the stomach (P = 0.006), right colon (P < 0.001) and small bowel (P = 0.035). A postresection perfusion deficit in the right colon with values below 254 perfusion units (PU) was identified as an independent predictor of clinically relevant complications after major hepatectomy (concordance index: 0.79, 95%CI 0.66-0.87, P = 0.002). Bootstrap validation confirmed internal validity and excellent calibration.

CONCLUSIONS: Major hepatectomy causes significant reduction of splanchnic perfusion. An intraoperative posthepatectomy microcirculatory perfusion deficit of the right colon is a strong and independent predictor of clinically relevant postoperative complications after major hepatectomy.

PMID:34856068 | DOI:10.1002/jhbp.1089

Anaesthesia. 2021 Dec 1. doi: 10.1111/anae.15626. Online ahead of print.

ABSTRACT

Videolaryngoscopes are thought to improve glottic view and facilitate tracheal intubation compared with the Macintosh direct laryngoscope. However, we currently do not know which one would be the best choice in most patients undergoing anaesthesia. We designed this systematic review with network meta-analyses to rank the different videolaryngoscopes and the Macintosh direct laryngoscope. We conducted searches in PubMed and a further five databases on 11 January 2021. We included randomised clinical trials with patients aged ≥16 years, comparing different videolaryngoscopes, or videolaryngoscopes with the Macintosh direct laryngoscope for the outcomes: failed intubation; failed first intubation attempt; failed intubation within two attempts; difficult intubation; percentage of glottic opening seen; difficult laryngoscopy; and time needed for intubation. We assessed the quality of evidence according to GRADE recommendations and included 179 studies in the meta-analyses. The C-MAC and C-MAC D-Blade were top ranked for avoiding failed intubation, but we did not find statistically significant differences between any two distinct videolaryngoscopes for this outcome. Further, the C-MAC D-Blade performed significantly better than the C-MAC Macintosh blade for difficult laryngoscopy. We found statistically significant differences between the laryngoscopes for time to intubation, but these differences were not considered clinically relevant. The evidence was judged as of low or very low quality overall. In conclusion, different videolaryngoscopes have differential intubation performance and some may be currently preferred among the available devices. Furthermore, videolaryngoscopes and the Macintosh direct laryngoscope may be considered clinically equivalent for the time taken for tracheal intubation. However, despite the rankings from our analyses, the current available evidence is not sufficient to ensure significant superiority of one device or a small set of them over the others for our intubation-related outcomes.

PMID:34855986 | DOI:10.1111/anae.15626

Pediatr Allergy Immunol. 2021 Dec 2. doi: 10.1111/pai.13709. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical presentations of coronavirus disease 2019 (COVID-19) among children with asthma have rarely been investigated. This study aimed to assess clinical manifestations and outcome of COVID-19 among children with asthma, and whether the use of asthma medications was associated with outcomes of interest.

METHODS: The Global Asthma Network (GAN) conducted a global survey among GAN centres. Data collection was between November 2020 and April 2021.

RESULTS: Fourteen GAN centres from 10 countries provided data on 169 children with asthma infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was asymptomatic in 58 (34.3%), mild in 93 (55.0%), moderate in 14 (8.3%) and severe/critical in 4 (2.4%). Thirty-eight (22.5%) patients had exacerbation of asthma and 21 (12.4%) were hospitalized for a median of 7 days (interquartile range 3-16). Those who had moderate or more severe COVID-19 were significantly more likely to have exacerbation of asthma as compared to those who were asymptomatic or had mild COVID-19 (adjusted odds ratio (adjOR) 3.97, 95% CI 1.23-12.84). Those who used inhaled bronchodilators were significantly more likely to have a change of asthma medications (adjOR 2.39, 95% CI 1.02-5.63) compared to those who did not. Children who used inhaled corticosteroids (ICS) did not differ from those who did not use ICS with regards to being symptomatic, severity of COVID-19, asthma exacerbation and hospitalization.

CONCLUSIONS: Over dependence on inhaled bronchodilator may be inappropriate. Use of ICS may be safe and should be continued in children with asthma during the pandemic of COVID-19.

PMID:34856034 | DOI:10.1111/pai.13709