Tag: statistics

Int Urol Nephrol. 2023 Jan 31. doi: 10.1007/s11255-023-03470-y. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) has become a major public health problem across the globe, leading to various complications. This study aimed to construct a nomogram to predict the 4-year risk of CKD among Chinese adults.

METHODS: The study was based on the China Health and Retirement Longitudinal Study (CHARLS). A total of 3562 participants with complete information in CHARLS2011 and CHARLS2015 were included, and further divided into the training cohort and the validation cohort by a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to select variables of the nomogram. The nomogram was evaluated by receiver-operating characteristic curve, calibration plots, and decision curve analysis (DCA).

RESULTS: In all, 2494 and 1068 participants were included in the training cohort and the validation cohort, respectively. A total of 413 participants developed CKD in the following 4 years. Five variables selected by multivariate logistic regression were incorporated in the nomogram, consisting of gender, hypertension, the estimated glomerular filtration rate (eGFR), hemoglobin, and Cystatin C. The area under curve was 0.809 and 0.837 in the training cohort and the validation cohort, respectively. The calibration plots showed agreement between the nomogram-predicted probability and the observed probability. DCA indicated that the nomogram had potential clinical use.

CONCLUSIONS: A predictive nomogram was established and internally validated in aid of identifying individuals at increased risk of CKD.

PMID:36720744 | DOI:10.1007/s11255-023-03470-y

Herz. 2023 Jan 31. doi: 10.1007/s00059-023-05163-9. Online ahead of print.

ABSTRACT

OBJECTIVE: Our aim was to determine the risk factors of postoperative systemic inflammatory response syndrome (SIRS) in patients with transcatheter aortic valve replacement (TAVR), identify those with a high risk of SIRS, and help reduce SIRS occurrence.

METHODS: A retrospective cohort study was conducted to collect the clinical data of patients who underwent TAVR from January 2014 to December 2019 at a tertiary hospital in Zhejiang Province. The study included 156 men and 94 women. Patients were divided into SIRS and non-SIRS groups. The pre-, intra-, and postoperative indices of the two groups were recorded. The data of the two groups were compared, and univariate analysis was performed. All statistically significant factors were assessed using binary logistic regression analysis to clarify the risk factors of SIRS after TAVR.

RESULTS: Overall, 30 patients developed SIRS after TAVR, with an incidence rate of 12%, an odds ratio (OR) of 0.571, and a 95% confidence interval (CI) of 0.469-0.694 (p = 0.000). There was a significant correlation between SIRS and glucose (OR: 0.823, 95% CI: 0.678-1.000, p = 0.049), albumin (OR: 0.938, 95% CI: 0.881-0.998, p = 0.044), brain natriuretic peptide (OR: 1.000, 95% CI: 1.000-1.000, p = 0.010), sex (OR: 0.412, 95% CI: 0.190-0.892, p = 0.025), and history of hypertension (OR: 0.375, 95% CI: 0.169-0.819, p = 0.014). Multivariate regression analysis demonstrated that age (OR: 1.190, 95%CI: 1.073-1.319, p = 0.001) and body mass index (BMI; OR: 0.559, 95% CI: 0.447-0.698, p = 0.000) were independent risk factors for postoperative SIRS in patients with TAVR.

CONCLUSION: The incidence of SIRS after TAVR was 12%. There was a significant correlation between SIRS and albumin, glucose, and hypertension. The independent risk factors for SIRS after TAVR were age and BMI.

PMID:36720725 | DOI:10.1007/s00059-023-05163-9

Orthop Surg. 2023 Jan 31. doi: 10.1111/os.13608. Online ahead of print.

ABSTRACT

OBJECTIVE: Wear particles induce inflammation and the further osteolysis around the prosthesis, has been proven to be the main cause of aseptic hip joint loosening. In this research, we aimed to clarify whether human umbilical cord mesenchymal stem cells (HUCMSCs) could inhibit the titanium particles-induced osteolysis and shed light upon its mechanism.

METHODS: The expression of chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5) were examinjed in clinical specimens of aseptic hip prosthesis loosening patients. Local injection of lentivirus that knocked down CCL2 or CCL3 in a cranial osteolysis mice model were used to exam the effect of CCL2 and CCL3 on titanium particles-induced osteolysis in vivo. Transwell assay was used to examine the effect of CCL2 and CCL3 on titanium particles-induced activation of macrophage in vitro. Furthermore, the therapeutic effect of HUCMSCs, and exosomes from HUCMSCs were also examed in vivo and vitro. Immunohistochemical and real-time PCR were used to examine the expression of relative pathways. Analysis of variance (ANOVA) and Student-Newman-Keuls post hoc t test were used to analyze the results and determine the statistical significance of the differences.

RESULTS: Results showed that titanium particles caused the osteolysis at the mice cranial in vivo and a large number of macrophages that migrated, while local injection of HUCMSCs and exosomes did inhibit the cranial osteolysis and migration. An exosome inhibitor GW4869 significantly increased the osteolysis area in the mice cranium osteolysis model, and increased the number of migrated macrophages. Immunohistochemical results suggested that the expression of CCL2, CCL3 and CD68 in the cranial in Titanium particles mice increased significantly, but was significantly reduced by HUCMSCs or exosomes. HUCMSC and exosomes down-regulate the expression of CCL3 in vitro and in vivo.

CONCLUSION: HUCMSCs and HUCMSC-derived exosomes could suppress the titanium particles-induced osteolysis in mice through inhibiting chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 3.

PMID:36720704 | DOI:10.1111/os.13608

Arab J Gastroenterol. 2023 Jan 29:S1687-1979(23)00005-9. doi: 10.1016/j.ajg.2023.01.004. Online ahead of print.

ABSTRACT

BACKGROUND AND STUDY AIMS: Intestinal metaplasia (IM), and Helicobacter pylori (HP) infection can be shown as risk factors in the development of gastric cancer (GC). WNT signaling pathway plays a critical role in carcinogenesis. However, the literature studies are limited on the significance of this pathway for the transition from IM to GC.

PATIENTS AND METHODS: We aimed to investigate the importance of the genes of WNT signaling pathways diagnostic and prognostic markers in the presence and absence of HP in conversion from IM to GC. 104 patients, (GC group n = 35, IM group n = 45, control group n = 25) were included in this case-control study. Expression of genes in WNT signalling were searched in study groups with qRT-PCR array and qRT-PCR method. Data were analysed using PCR array data analysis software.

RESULTS: Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in the GC and IM groups compared to the control group (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was observed in patients with metastatic GC compared to patients with GC without metastasis (p < 0.05). It was found that the RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes were statistically significantly over-expressed in diffuse GC patients compared to non-diffuse GC patients (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in HP positive IM patients compared to HP negative IM patients (p < 0.05).

CONCLUSION: Overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes in IM may suggest that these genes are important markers in the development of IM and inflammation with HP. In addition, these genes are linked to tumor burden in the GC group. Consequently, we can conclude that these genes are poor prognosis biomarkers for GC and have the potential to be used as markers for future treatment monitoring.

PMID:36720664 | DOI:10.1016/j.ajg.2023.01.004

Eur Urol Oncol. 2023 Jan 29:S2588-9311(23)00028-7. doi: 10.1016/j.euo.2023.01.010. Online ahead of print.

ABSTRACT

BACKGROUND: The extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival.

OBJECTIVE: To perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups.

DESIGN, SETTING, AND PARTICIPANTS: CLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC.

INTERVENTION: Patients were randomized 1:1:1 to lenvatinib 20 mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Landmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1.

RESULTS AND LIMITATIONS: Landmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or >75% target-lesion reduction by 6 mo had a 24-mo OS probability of ≥91.7%. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4% vs 28.8%) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified.

CONCLUSIONS: Lenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS.

PATIENT SUMMARY: In this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a “complete response” or had their tumors shrunk by >75% within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib.

PMID:36720658 | DOI:10.1016/j.euo.2023.01.010

Comput Methods Programs Biomed. 2023 Jan 23;231:107366. doi: 10.1016/j.cmpb.2023.107366. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Computer simulations of joint contact mechanics have great merit to improve our current understanding of articular ankle pathology. Owed to its computational simplicity, discrete element analysis (DEA) is an encouraging alternative to finite element analysis (FEA). However, previous DEA models lack subject-specific anatomy and may oversimplify the biomechanics of the ankle. The objective of this study was to develop and validate a personalized DEA framework that permits movement of the fibula and incorporates personalized cartilage thickness as well as ligamentous constraints.

METHODS: A linear and non-linear DEA framework, representing cartilage as compressive springs, was established, verified, and validated. Three-dimensional (3D) bony ankle models were constructed from cadaveric lower limb CT scans imaged during application of weight (85 kg) and/or torque (10 Nm). These 3D models were used to generate cartilage thickness and ligament insertion sites based on a previously validated statistical shape model. Ligaments were modelled as non-linear tension-only springs. Validation of contact stress prediction was performed using a simple, axially constrained tibiotalar DEA model against an equivalent FEA model. Validation of ligamentous constraints compared the final position of the ankle mortise to that of the cadaver after application of torque and sequential ligament sectioning. Finally, a combined ligamentous-constraining DEA model was validated for predicted contact stress against an equivalent ligament-constraining FEA model.

RESULTS: The linear and non-linear DEA model reproduced a mean articular contact stress within 0.36 MPa and 0.39 MPa of the FEA calculated stress, respectively. With respect to the ligamentous validation, the DEA ligament-balancing algorithm could reproduce the position of the distal fibula within the ankle mortise to within 0.97 mm of the experimental observed distal fibula. When combining the ligament-constraining and contact stress algorithm, DEA was able to reproduce a mean articular contact stress to within 0.50 MPa of the FEA calculated contact stress.

CONCLUSION: The DEA framework presented herein offers a computationally efficient alternative to FEA for the prediction of contact stress in the ankle joint, manifesting its potential to enhance the mechanical understanding of articular ankle pathologies on both a patient-specific and population-wide level. The novelty of this model lies in its personalized nature, inclusion of the distal tibiofibular joint and the use of non-linear ligament balancing to maintain the physiological ankle joint articulation.

PMID:36720186 | DOI:10.1016/j.cmpb.2023.107366

J Neural Eng. 2023 Jan 31. doi: 10.1088/1741-2552/acb79f. Online ahead of print.

ABSTRACT

Intracranial EEG (iEEG) plays a critical role in the treatment of neurological diseases, such as epilepsy and Parkinson’s disease, as well as the development of neural prostheses and brain computer interfaces. While electrode geometries vary widely across these applications, the impact of electrode size on iEEG features and morphology is not well understood. Some insight has been gained from computer simulations, as well as experiments in which signals are recorded using electrodes of different sizes concurrently in different brain regions. Here, we introduce a novel method to record from electrodes of different sizes in the exact same location by changing the size of iEEG electrodes after implantation in the brain. We first present a theoretical model and an in vitro validation of the method. We then report the results of an in vivo implementation in three human subjects with refractory epilepsy. We recorded iEEG data from three different electrode sizes and compared the amplitudes, power spectra, inter-channel correlations, and signal-to-noise ratio (SNR) of interictal epileptiform discharges, i.e., epileptic spikes. We found that iEEG amplitude and power decreased as electrode size increased, while inter-channel correlation did not change significantly with electrode size. The SNR of epileptic spikes was generally highest in the smallest electrodes, but 39% of spikes had maximal SNR in larger electrodes. This likely depends on the precise location and spatial spread of each spike. Overall, this new method enables multi-scale measurements of electrical activity in the human brain that can facilitate our understanding of neurophysiology, treatment of neurological disease, and development of novel technologies.

PMID:36720162 | DOI:10.1088/1741-2552/acb79f

Biomed Mater. 2023 Jan 31. doi: 10.1088/1748-605X/acb7bd. Online ahead of print.

ABSTRACT

The goal of this study is to fabricate biocompatible and minimally invasive bone tissue engineering scaffolds that allow in situ photocuring and further investigate the effect on the mechanical properties of the scaffold due to the prevailing conditions around defect sites, such as the shift in pH from the physiological environment, swelling due to accumulation of fluids during inflammation, etc. A novel approach of incorporating a general full factorial Design of Experiment (DOE) model to study the effect of the local environment of the tissue defect on the mechanical properties of these injectable and photocurable scaffolds has been formulated. Moreover, the cross-interaction between factors, such as pH and immersion time, was studied as an effect on the response variable. This study encompasses the fabrication, and uniaxial mechanical testing of polyethylene glycol dimethacrylate (PEGDMA) scaffolds for injectable tissue engineering applications, along with the loss in weight of the scaffolds over 72 h in a varying pH environment that mimics in vivo conditions around a defect. The DOE model was constructed with three factors: the combination of PEGDMA and nanohydroxyapatite, referred to as biopolymer blend, the pH of the buffer solution used for immersing the scaffolds, and the immersion time of the scaffolds in the buffer solution. The response variables recorded were compressive modulus, compressive strength, and the weight loss of the scaffolds over 72 h of immersion in phosphate-buffered saline at respective pH. The statistical model analysis provided adequate information in explaining a strong interaction of the factors on the response variables. Further, it revealed a significant cross-interaction between the factors. The factors such as the biopolymer blend and pH of the buffer solution significantly affected the response variables, compressive modulus, and strength. At the same time, the immersion time had a strong effect on the loss in weight from the scaffolds over 72 h of soaking in the buffer solution. The biocompatibility study done using a set of fluorescent dyes for these tissue scaffolds highlighted an enhancement in the preosteoblasts (OB-6) cell attachment over time up to day 14. The representative fluorescent images revealed an increase in cell attachment activity. This study has opened a new horizon in optimizing the factors represented in the DOE model for tunable PEGDMA-based injectable scaffold systems with enhanced bioactivity.

PMID:36720161 | DOI:10.1088/1748-605X/acb7bd

JMIR Public Health Surveill. 2023 Jan 30. doi: 10.2196/34579. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has challenged public health efforts globally. Timely population-based surveillance is crucial to support public health programs and policies to limit the spread of COVID-19. In South Carolina (SC), the SC STRONG state-wide initiative was established to estimate population-level prevalence and immunity and characterize the transmission dynamics of the SARS-CoV-2 virus using community testing and online surveys.

OBJECTIVE: This paper aimed to leverage the survey data collected as part of the initiative to understand risk perceptions, testing practices and preventive behaviors, and identify risk factors for COVID-19 test positivity in SC over time.

METHODS: Probability proportionate to size cluster random sampling was used to select SC residents to participate in testing for COVID-19 infection and antibodies, and to complete an online survey. This paper focuses on data from the online surveys completed between November 2020 and June 2021. Descriptive statistics were performed to describe risk perceptions, attitudes and behaviors, and associated changes over time. Univariate and multivariate logistic regression models were used to identify factors associated with self-reported COVID-19 test positivity.

RESULTS: Among the 7,170 online survey respondents, 58.7% self-reported ever testing for COVID-19. The most commonly cited barriers to testing were inconvenient dates, time, and location and discomfort. Overall, 18.7% of respondents reported a history of COVID-19 test positivity. Multivariate logistic regression results indicated that individuals who were 50 years and older, self-identified as Black/African American, obese, and employed as frontline health care workers and nursing home staff were more likely to self-report COVID-19 test positivity. By contrast, there was a decreased likelihood of test positivity among respondents who were concerned about the burden of COVID-19 in their community and about getting infected.

CONCLUSIONS: Strategies to remove testing barriers should be implemented to improve access. Findings provide insights on statewide testing patterns, adoption of prevention behaviors and risk factors for infection and may inform public health strategies to curb transmission.

PMID:36720159 | DOI:10.2196/34579

N Engl J Med. 2023 Jan 26;388(4):299-309. doi: 10.1056/NEJMoa2204511.

ABSTRACT

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive.

METHODS: In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis.

RESULTS: Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups.

CONCLUSIONS: In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).

PMID:36720132 | DOI:10.1056/NEJMoa2204511