Safety Ranking Research Articles

Development of a Comprehensive Safety Evaluation Mechanism for the Highway Bus Industry

A suitable mechanism for evaluating the safety of the highway bus industry is crucial for ensuring public transportation safety in a country. In this study, we have combined indices from the Compliance Safety Accountability (CSA) program of the Federal Motor Carrier Safety Administration (FMCSA) in the US, the safety evaluation of renting buses in Japan, and some existing safety evaluation methods in Taiwan to develop a new safety evaluation mechanism for the highway bus industry. This paper introduces a two-stage decision making approach that includes the use of fuzzy analytic hierarchy process (Fuzzy AHP) and machine learning techniques such as decision trees, support vector machines, and random forests to develop this mechanism. The data used in this research were collected from the internet and directly from highway bus transportation companies. We calculated the safety performance of each company and assigned them different safety ranks. Compared with the causes of accidents in Taiwan, the results of this study showed that work hours, driver fitness, and administrative penalties are the three most important sub-attributes that affect the safety rank of the company.

Efficacy and safety of Vonoprazan-based treatment of Helicobacter pylori infection: a systematic review and network meta-analysis

ObjectiveThe aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection.DesignThrough searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly.ResultsThe RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety.ConclusionCompared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.

Comparative safety of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis.

To indirectly compare the safety of immune checkpoint inhibitors (ICIs) in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by network meta-analysis (NMA). Through August 1, 2023, we searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for randomized clinical trials (RCTs) of ICI-based treatment for R/M HNSCC. Outcomes of interest included overall and organ-specific immune-related adverse events (irAEs). Addis 16.5 software was used to perform NMA. Confidence in Network Meta-Analysis (CINeMA) was used to assess confidence in the evidence. Nine RCTs were included in this NMA, involving a total of 4016 patients. The general safety of ICI-based treatments in descending order was as follows: Durvalumab + Tremelimumab, Camrelizumab + Chemotherapy, Durvalumab, Toripalimab + Chemotherapy, Pembrolizumab, Pembrolizumab + Chemotherapy, Nivolumab, Tremelimumab. There were differences in the toxicity profile among Toripalimab + Chemotherapy (dermatologic irAEs), Camrelizumab + Chemotherapy (hypothyroidism), Nivolumab + Ipilimumab (hyperthyroidism, pneumonitis), Pembrolizumab (nephrotoxicity), Pembrolizumab + Chemotherapy (colitis). ICI-based treatment increased the incidence of endocrine irAEs (hyperthyroidism and hypothyroidism) and pneumonitis compared to conventional therapy. Besides, the combination of dual ICIs resulted in a greater occurrence of irAEs compared to the use of a single ICI. The safety ranking of treatments based on ICIs is significantly influenced by specific irAEs. These irAEs, which vary in type and severity, play a crucial role in determining the overall safety profile of each ICI regimen. PROSPERO CRD42023460267.

Assessment of truck driver safety efficiency based on data envelopment analysis

This paper introduces a safety efficiency evaluation framework that integrates Data Envelopment Analysis (DEA) and Super-Efficiency Data Envelopment Analysis (SE-DEA) for quantitatively assessing the safety of truck drivers. The framework utilizes data from onboard equipment to capture drivers’ dangerous behaviors and poor driving states. Subsequently, it evaluates safety efficiency using the DEA combination model, providing safety rankings. Improvement suggestions are offered to underperforming drivers based on slack variable values. The proposed method is compared with EWM-Topsis and Critic-Topsis models using fixed weights, demonstrating better stability. The study’s outcomes enable freight companies to identify high-risk drivers and offer personalized, targeted safety training.

The Spatial Interface of Informal Settlements to Women’s Safety: A Human-Scale Measurement for the Largest Urban Village in Changsha, Hunan Province, China

Building sustainable communities is always related to the occupants’ physical and psychological safety, environmental security and human settlements inclusivity, etc. The interfaces of Chinese urban villages have shown features that are irregular and chaotic, which led to potential safety hazards for women. This study revealed the blind spot of how environmental interfaces affect women’s safety and proposed interface micro-renewal strategies that would have sustainable positive impacts on the safety of vulnerable populations in the future. Taking the largest urban village in Changsha as a case study, a total of 764 samples were collected from human-scale surveys and interviews; t-tests and various regression models were adopted to explore the correlation of nine interface variables on their safety perception. Multiple equations were constructed through ANOVA analysis and the machine learning model (ROC). The results show that interfaces have a strong association with women’s perceived safety compared to men, especially women aged 41–55 who were not engaged and had manual work at night. The safety ranking of variables follows the penetrability > proximity > scale, but it shows differences in terms of work type and age. This study would provide the necessary research to complement a sustainable urban transition and gender equality in the informal settlements of the Global South.

Safety profile evaluation of different herbicides used on peach rootstock seedlings.

To screen out suitable herbicides for peach nurseries, we treated the potted seedlings of the peach rootstock 'Nemaguard' with eleven herbicides under recommended doses to investigate the changes of physiological indices and comprehensively evaluate the safety of different herbicides using principal component analysis (PCA). The results showed that soil application of quizalofop-p exhibited no detectable phytotoxicity on rootstock seedlings, while the remaining herbicides generated multiple symptoms, including green loss, wilting, spot, and withering. Starane caused rapid wilting and death, with a 100.0% phytotoxicity index (PI). Soil application of n-(phosphonomethyl)glycine, glufosinate-ammonium, acetochlor, and MCPA-Na showed a PI＞65.0%. As compared with the control, all herbicides inhibited leaf area growth to varying degrees, with a 10.0%-56.2% and 5.8%-44.4% reduction in young leaf area and mature leaf area, respectively. All herbicides, except quizalofop-p, increased the electrolyte permeability of leaf and root tip cells by 21.2%-145.0% and 36.9%-291.4%, respectively, and significantly inhibited root growth. The total root length, root surface area, root volume, and the number of root tips significantly decreased by 37.3%-75.3%, 35.7%-83.0%, 44.3%-89.9%, and 42.6%-73.7%, respectively. Although net photosynthetic rate (Pn) and transpiration rate (Tr) of leaves were not significantly affected by quizalofop-p, mesotrione-atrazine, MCPA-Na·bentazone, bensulfuron-methyl·quinclorac, and bensulfuron-methyl·acetochlor, there was significant reduction of 29.6%, 28.9%, 28.4% and 27.9% in Pn and 21.9%, 29.2%, 26.4%, and 19.7% in Tr post soil application of n-(phosphonomethyl)glycine, glufosinate-ammonium, acetochlor, and MCPA-Na. The overall safety ranking of the 11 examined herbicides is as follows: quizalofop-p>bensulfuron-methyl·acetochlor>bensulfuron-methyl·quinclorac>esotrione·atrazine> auizalofop-p·fluoroglycofen>acetochlor>MCPA-Na·bentazone>MCPA-Na>n-(phosphonomethyl)glycine>glufosinate-ammonium>sterane.

Inherent safety of clean fuels for maritime transport

The urgent need to reduce the emission of harmful pollutants in maritime transport promoted the development of several alternative propulsion systems based on clean fuels or carbon-neutral energy vectors. However, the alternative solutions under development pose new concerns from the safety perspective. Thus, an innovative methodology to rank the inherent safety performance of alternative systems at early design stages was developed. A case study representative of long-distance maritime transportation was analysed. The inherent safety performances of Liquefied Natural Gas (LNG), Liquid Hydrogen (LH2), and Liquid Ammonia (LNH3) were compared to that of Marine Gas Oil (MGO), assumed as a benchmark representing state-of-the-art technologies. Uncertainty and robustness of the safety ranking obtained were tested via a Monte Carlo analysis. The results show that technologies based on LNG have similar safety performances with respect to the benchmark option. Conversely, LH2 safety performance is currently limited by the lack of mature technologies for its safe storage whilst the safety of LNH3-based applications is affected by the toxicity of ammonia.

Hepatotoxicity of immune checkpoint inhibitors: What is Currently Known

This systematic review and network meta-analysis aimed to provide a complete hepatotoxicity profile, hepatotoxicity spectrum, and safety ranking of immune checkpoint inhibitor drugs for cancer treatment. PubMed, Embase, Scopus, CINAHL, Web of Science, psycINFO, Cochrane Library, and ClinicalTrials.gov. websites were searched, and a manual search of relevant reviews and trials up to January 1, 2022, was undertaken. Head-to-head III randomized controlled trials comparing any 2 or 3 of the following treatments or different doses of the same immune checkpoint inhibitor drug were included: programmed death 1 (PD-1), programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors and conventional therapy. We included 106 randomized trials (n=164,782) containing 17 treatment arms. The overall incidence of hepatotoxicity was 4.06%. The rate of fatal liver adverse events was 0.07%. The programmed death ligand 1 inhibitor+targeted therapy drug+chemotherapy group had the highest risk of treatment-related increases in all-grade alanine aminotransferase and aspartate aminotransferase levels, and the differences were significant. For immune-related hepatotoxicity, no significant difference was found between PD-1 and CTLA-4 inhibitors for all-grade hepatotoxicity; however, CTLA-4 inhibitors were associated with a higher risk of grade 3-5 hepatotoxicity than PD-1 inhibitors. The highest incidence of hepatotoxicity and fatality was observed with triple therapy. The overall incidence of hepatotoxicity was similar between different dual regimens. For immune checkpoint inhibitor monotherapy, the overall risk of immune-mediated hepatotoxicity related to CTLA-4 inhibitors did not differ significantly from that of PD-1 inhibitors. There was no direct relationship between the risk of liver injury and drug dose, whether monotherapy or combination therapy was used.

The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis.

Combination treatment regimens consisting of both immune checkpoint inhibitors (ICI) and chemotherapeutic agents have emerged as the standard of care for a range of cancers. This network meta-analysis (NMA) examined the toxicity profiles and safety rankings of these different ICI-based combination regimens. The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for all randomized controlled trials (RCTs) published as of March 1, 2022 comparing two or more treatment regimens in which at least one arm was comprised of an ICI + platinum-based chemotherapeutic regimen. Treatment-related adverse events (AEs) of any grade and AEs of grade 3 or higher were the primary endpoints for this analysis, while specific AE types were secondary endpoints. This NMA combined both direct and indirect comparisons when analyzing odds ratios (ORs) and the surface under the cumulative ranking curve (SUCRA) for different ICI-based treatment regimens. In total, 33 RCTs enrolling 19,012 cancer patients were included in this NMA. Of the analyzed regimens, avelumab + chemotherapy and camrelizumab + chemotherapy were associated with a significantly greater risk of AEs of any grade relative to ipilimumab + chemotherapy, durvalumab + chemotherapy, or pembrolizumab + chemotherapy. No significant differences in the risk of AEs of grade 3 or higher were observed when comparing different ICI regimens. Hepatotoxicity and pyrexia were the most common AEs associated with atezolizumab + chemotherapy treatment. Ipilimumab + chemotherapy was associated with a relatively higher risk of gastrointestinal and skin toxicity. Skin toxicity and hypothyroidism were the major AEs associated with nivolumab + chemotherapy. Fatigue and pneumonia were the most common AEs respectively associated with sugemalimab + chemotherapy and pembrolizumab + chemotherapy regimens. Of the evaluated regimens, camrelizumab + chemotherapy and avelumab + chemotherapy were associated with significantly higher rates of AEs of any grade, whereas durvalumab and sintilimab were relatively safe PD-L1 and PD-1 inhibitors, respectively, when administered in combination with platinum-based chemotherapy. However, none of the evaluated ICI + chemotherapy regimens exhibited any differences with respect to the incidence of grade 3 or higher AEs, offering guidance that may be of value in routine clinical practice.

The Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis.

The eradication of Helicobacter pylori (H. pylori) infection remains challenging due to increasing bacterial resistance. Resistance rates to clarithromycin, metronidazole, and levofloxacin were higher than 30% in the USA, making current therapies less effective. Vonoprazan triple therapy (VAC) has demonstrated similar efficacy and safety profiles compared to PPI-based triple therapy (PPI). However, the eradication rate of vonoprazan dual therapy (VA) for H. pylori infection in comparison to VAC, and PPI was poorly established. Electronic databases were searched up to 6 October 2022, to identify studies examining the safety and efficacy of VA compared to VAC and PPI. Six studies were included. For empiric therapies among treatment naïve patients, VA, VAC, and PPI did not achieve high cure rates (>90%). The comparative efficacy ranking showed VAC was the most effective therapy, followed by VA, and PPI. The results were similar for clarithromycin-resistant infections. The comparative safety ranking showed VA ranked first, whereas PPI triple therapy was the least safe regimen. These findings should guide the selection of the most effective and safe treatment and conduct additional studies to determine the place of vonoprazan dual versus triple therapies in patients with H. pylori from various countries across the world.

Optimizing targeted drug selection in combination therapy for patients with advanced or metastatic renal cell carcinoma: A systematic review and network meta-analysis of safety.

For patients with advanced or metastatic renal cell carcinoma (RCC), the dose of targeted agents was recommended in combination with immune checkpoint inhibitors. We performed a network meta-analysis to describe a categorized safety ranking profile and assess the adaptability of the combination options of targeted agents. The targeted agents refer to vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Randomized controlled trials comparing these drugs were enrolled in a Bayesian model network meta-analysis. Nineteen clinical trials with 11 treatments and 10,615 patients were included. For grade≥ 3 adverse events (AEs), compared with placebo, lenvatinib plus everolimus showed worse safety than all other treatments except for lenvatinib (placebo vs. OR 0.23, 95% CI 0.07-0.78). Everolimus was generally the safest agent (OR 1.23, 95% CI 0.50-3.14). Sorafenib arose the least renal AEs (placebo vs. OR 0.85, 95% CI 0.06-11.64), whereas lenvatinib plus everolimus had the highest risk of renal toxicity (placebo vs. 0.17 95% CI 0.01-1.02). For gastrointestinal symptoms, everolimus was related to much lower toxicity than other agents. In the respiratory safety analysis, tivozanib (placebo vs. OR 0.15, 95% CI 0.07-0.31) and axitinib (OR 5.43, 95% CI 3.26-9.22) were the riskiest agents. In terms of hepatobiliary (placebo vs. OR 0.44, 95% CI 0.09-2.10) and hemotoxicity (placebo vs. OR 1.03, 95% CI 0.14-7.68) related AEs, lenvatinib was found to be the safest treatment compared to placebo. Everolimus, with the best safety of grade≥ 3, gastrointestinal, and respiratory AEs, was more likely to be considered for combination therapies. Lenvatinib appears to be the safest for blood/lymphatic and hepatobiliary AEs. For patients with renal disorders, sorafenib arises the least renal toxicity AEs. This study will guide treatment options and optimize the trial design for advanced or metastatic RCC.

Assessment of Railway Safety in Southeast Asia Region

This paper reports on the railway safety in Southeast Asia based on rail accidents and incidents trends. Rail transportation has many benefits, it includes fixed routes, cost-effective, safe and large capacity. It is also every country's major means of transportation. However, there are less research on causes of rail accidents and incidents, despite rail risk assessments being conducted in Great Britain, Finland and Japan.
 In Southeast Asia, there is no investigation for predicting rail accidents and incidents. Hence, it is vital to study the railway safety risks in this region. Data reporting is based on news or reports published for public reviews. After performing Trend Analysis, robustness is evaluated in prior to perform risk analysis using Delphi technique. Following risk analysis, the Analytic Hierarchy Process (AHP) technique-based railway safety rank is carried out which is designed by the Authors of this study. The variables are based on total number of cases and fatalities, level of robustness and risk. Ranking countries from high-risk to low-risk, the rank are as follows; Thailand, Indonesia, Vietnam, Myanmar, Philippines, Malaysia, Cambodia and Singapore.

Aviation safety ranking values and bird species at Trabzon International Airport, Türkiye

The study investigated bird species at Trabzon International Airport (TIA) in Türkiye and their Aviation Safety Ranking Values (ASRV). During the study period between February 2021 and February 2022, 75 observations were carried out using direct and indirect observation methods (camera traps, bird nests, eggs, feathers and; pellets) to identify species. As a result, 109 bird species were identified belonging to 39 families. Migration status of the observed birds ranged from overwintering (27), to summer visitors (26), residents (17), wintering and passage migrants (14), passage migrants (9), residents and wintering (8), residents and summer visitors (5), and residents and passage migrants (3). The bird hazard ranking system is based on bird size, average weights, flocking characteristics, and flight behaviour. According to the criteria of the ASRV, a total of 36 bird species at TIA with hazard levels of intermediate (3), high (4), and very high (5) were determined. Among the species identified, 25 weighed between 700 and 2200 grams. Wildlife professionals should be assigned to all airports to successfully control bird strikes and increase flight safety, and bird observations should be performed regularly.

Briefs

University to pay family of victim nearly $1 million Michigan finalizes settlement with abuse victims University moves forward with private, armed police force University offers safety rankings of off‐campus rentals

Novel Insights into the Inheritance of Gibberella Ear Rot (GER), Deoxynivalenol (DON) Accumulation, and DON Production.

Gibberella ear rot (GER) is an important fungal ear pathogen of maize that causes ear rot and toxin contamination. Most previous works have only dealt with the visual symptoms, but not with the toxins of GER. As food and feed safety rankings depend on toxin contamination, including deoxynivalenol (DON), without toxins, nothing can be said about the risks involved in food and feed quality. Therefore, three susceptible, three medium-susceptible, and three medium-resistant mother lines were crossed with three testers with differing degrees of resistance and tested between 2017–2020. Two plot replicates and two fungal strains were used separately. The highest heterosis was found at the GER% with a 13% increase across 27 hybrids, including 7 hybrids showing negative heterosis (a higher hybrid performance above the parental mean), with a variance ranging between 63.5 and −55.4. For DON, the mean heterosis was negative at −35%, and only 10 of the 27 hybrids showed a positive heterosis. The mean heterosis for DON contamination, at 1% GER, was again negative (−19.6%, varying between 85% and 224%). Only 17 hybrids showed heterosis, while that of the other 17 was rated higher than the parental mean. A positive significant correlation was found only for GER% and DON; the other factors were not significant. Seven hybrids were identified with positive (2) or negative (5) heterosis for all traits, while the rest varied. For DON and GER, only 13 provided identical (positive or negative) heteroses. The majority of the hybrids appeared to diverge in the regulation of the three traits. The stability of GER and DON (variance across eight data sets) did not agree—only half of the genotypes responded similarly for the two traits. The genetic background for this trait is unknown, and there was no general agreement between traits. Thus, without toxin analyses, the evaluation of food safety is not possible. The variety in degrees of resistance to toxigenic fungi and resistance to toxin accumulation is an inevitable factor.

Comparative safety of immune checkpoint inhibitors and chemotherapy in advanced non-small cell lung cancer: A systematic review and network meta-analysis

BackgroundsImmune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the standard of care for first-line therapy in metastatic non-small cell lung cancer (NSCLC) patients without actionable mutations. The safety ranking of different ICI and CT combination regimens has not been investigated. This study was aimed to provide a toxicity profile and safety ranking of different ICI and CT combination regimens. MethodsWe performed comprehensive searches of phase 2 and 3 randomized clinical trials (RCTs) comparing different ICI regimens (alone or combination) or CT for the first-line treatment of advanced NSCLC. Outcomes of interest were the cumulative incidence of any treatment-related adverse events (TRAEs), grade 3–5 TRAEs (grade 3–5), any immune-related adverse events (irAEs), and grade 3–5 irAEs (grade 3–5). Odds ratios and 95% credible intervals were calculated as summary statistics to quantify the effect of different ICI combination regimens. ResultsWe included 21 RCTs from 2016 to 2021 with a total of 12,626 patients. The incidence of any TRAEs and grade 3–5 TRAEs ranked from high to low were ICI-CT (probability: 88.3% and 87.1%), ICI-ICI-CT (66.2% and 73.9%), CT alone (77.7% and 86.6%), ICI-ICI (98.9% and 99.2%), and ICI monotherapy (99.7% and 100%). Adding CT to ICI regimens resulted in a higher incidence of any grade or grade 3–5 TRAEs compared to ICI-ICI combinations or ICI monotherapy. However, ICI-ICI-CT combinations did not result in a higher incidence of TRAEs than ICI-CT combinations. For any irAEs and grade 3–5 irAEs, the ranking was ICI-ICI (probability: 97.6% and 99.8%), ICI monotherapy (97.2% and 99.8%), ICI-CT (99.5% and 99.9%), and CT alone (99.9% and 100%). Notably, the incidence of any grade and grade 3–5 irAEs was lower when adding CT to ICI monotherapy. ConclusionLack of head-to-head comparisons, these findings provide evidence for clinical decision-making when considering different ICI combination regimens for advanced NSCLC patients.

MP12-16 OPTIMIZING TARGETED DRUG SELECTION IN COMBINATION THERAPY FOR PATIENTS WITH ADVANCED OR METASTATIC RENAL CELL CARCINOMA: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF SAFETY

You have accessJournal of UrologyCME1 May 2022MP12-16 OPTIMIZING TARGETED DRUG SELECTION IN COMBINATION THERAPY FOR PATIENTS WITH ADVANCED OR METASTATIC RENAL CELL CARCINOMA: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF SAFETY Ruiyang Xie, Bingqing Shang, Weixing Jiang, Chuanzhen Cao, Hongzhe Shi, and Jianzhong Shou Ruiyang XieRuiyang Xie More articles by this author , Bingqing ShangBingqing Shang More articles by this author , Weixing JiangWeixing Jiang More articles by this author , Chuanzhen CaoChuanzhen Cao More articles by this author , Hongzhe ShiHongzhe Shi More articles by this author , and Jianzhong ShouJianzhong Shou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002534.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Targeted therapies were often applied in the combination with immune checkpoint inhibitors for patients with advanced or metastatic renal cell carcinoma (RCC). A network meta-analysis was carried out to provide a categorized safety ranking profile and assess the adaptability for combination choice of targeted therapies. METHODS: Randomized controlled trials comparing vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) and mammalian target of rapamycin (mTOR) inhibitors were included in a Bayesian network meta-analysis. RESULTS: 19 relevant trials with 10,615 patients and 11 treatments were included. For grade ≥3 adverse events, lenvatinib plus everolimus showed worse safety than other treatments except for lenvatinib when compared to placebo (placebo versus OR 0.23, 95% CI 0.07-0.78), whereas the OR of everolimus versus placebo was relatively low (OR 1.23, 95% CI 0.50-3.14). Temsirolimus was demonstrated to cause the most severe renal and urinary disorders compared to placebo (placebo versus OR 0.08, 95% CI 0.00-2.61) among the treatments, and lenvatinib plus everolimus was observed with a low OR of 0.17 95% CI 0.01-1.02 as well. In contrast, sorafenib showed an OR that was lower than 1 for renal and urinary disorders compared to other VEGF-TKIs. For gastrointestinal symptoms, lenvatinib was found to be correlated with much higher toxicity than other treatments. Tivozanib and axitinib were the worst two in terms of respiratory disorders, and all the OR values of other treatments were statistically significant except the comparison between these two. In terms of hepatobiliary disorders, cabozantinib was found to be the worst treatment compared to placebo (OR 9.33, 95% CI 3.78-28.56). CONCLUSIONS: Lenvatinib plus everolimus had the worst and the second worst in terms of adverse events related to renal disorders and grade ≥3 adverse events, respectively. Everolimus, with the best ranking of safety, was more likely to be selected for combination therapies. This study will guide treatment choice and optimize the future trial design for advanced or metastatic RCC. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e174 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ruiyang Xie More articles by this author Bingqing Shang More articles by this author Weixing Jiang More articles by this author Chuanzhen Cao More articles by this author Hongzhe Shi More articles by this author Jianzhong Shou More articles by this author Expand All Advertisement PDF DownloadLoading ...

Complementary and alternative therapies for stable angina pectoris of coronary heart disease: A protocol for systematic review and network meta-analysis.

Background:Stable angina pectoris in patients with coronary heart disease is a clinical syndrome of rapid transient ischemia and hypoxia of myocardium due to the increase of myocardial load on the basis of fixed severe coronary artery stenosis. In recent years, the incidence rate of this disease has been rising steadily, which seriously threatens human life and health. When the disease occurs, its complementary and alternative therapy can relieve chest pain, improve cardiac function, and reduce adverse events. However, in retrospect of all the studies, we lack systematic analysis of the efficacy and safety of various complementary and alternative therapies. The curative effects were ranked. On the basis of these findings, we conducted a study of complementary and alternative therapy in patients with coronary heart disease, and proposed a network meta-analysis (NMA) protocol to explore the efficacy of different complementary and alternative therapies.Methods:We will comprehensively search the Chinese and English databases from the creation date to January 15, 2022. The randomized controlled trials of the supplementary and alternative treatment of stable angina pediatrics in patients with coronary heart disease and the relevant literature of the ongoing trials will be published. The 2 researchers will conduct literature screening and data extraction independently, using Cochrane system evaluator manual 5 3. The recommended bias risk assessment tool was used to evaluate the quality of the included study, Q-test was used and combined with heterogeneity analysis, and the analysis sensitivity was observed. The Review Manager 5.4 software provided by Cochrane Collaboration Network is used to statistically analyze the included literature, and the obtained results are made into forest map and funnel map for data analysis and processing. It is suggested that the evaluation will be used to formulate and evaluate the level, so as to classify the quality of NMA evidence.Results:Through analysis, we will get the efficacy and safety ranking of different complementary and alternative therapies in the treatment of stable angina pediatrics in patients with coronary heart disease, so as to provide further reference for the selection of clinical treatment methods.Conclusion:The complementary and alternative treatment of stable angina peptis in patients with coronary heart disease has a positive effect on improving its symptoms. This study can provide evidence support for clinicians and patients.INPLASY registration number:INPLASY202210066.

Efficacy and safety of the combination of modern medicine and traditional Chinese medicine in pulmonary fibrosis caused by novel coronavirus disease: A protocol for Bayesian network meta-analysis.

Background:Novel coronavirus disease (COVID-19) is a kind of pulmonary inflammation induced by New Coronavirus. It seriously threatens people's health and safety. Clinical studies have found that some patients have different degrees of inflammation after discharge from hospital, especially in patients with severe inflammatory lung fibrosis. Early combination of Chinese medicine and modern medicine has important clinical significance. There are still many deficiencies in the current research. We studied the effectiveness of the combination of traditional Chinese medicine and modern medicine in the treatment of pulmonary fibrosis caused by COVID-19, and proposed a network meta-analysis (NMA) scheme.Methods:According to the search strategy, we will search Chinese and English databases to collect all randomized controlled trials of traditional Chinese medicine combined with modern drugs or only using traditional Chinese medicine for new coronavirus-19-induced pulmonary fibrosis between December 1, 2019 and November 15, 2021. First, the literature was screened according to the eligibility criteria, endnotex9 was used to manage the literature, and the Cochrane Collaboration's tool was used to assess the quality of the included literature. Revman 5.3, Stata 14.2, and gemtc14.3 meta-analysis software was then used for data processing and analysis, and the grading of recommendations assessment will be used to develop and evaluate a hierarchy for classifying the quality of evidence for NMA.Results:Through the analysis, the ranking of efficacy and safety of various treatments for pulmonary fibrosis caused by COVID-19 will be drawn, thus providing stronger evidence support for the choice of clinical treatment methods.Conclusion:Traditional Chinese medicine (TCM) combined with modern drugs has played a positive role in the treatment of pulmonary fibrosis caused by COVID-19, and this study may provide more references for the clinical medication of pulmonary fibrosis caused by COVID-19.INPLASY registration number:INPLASY2021110061.

Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Advanced Non-small Cell Lung Cancer: A Network Meta-Analysis of Randomized Clinical Trials.

Objective: This network meta-analysis will provide a complete toxicity profile, toxicity profile, and safety ranking of immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC). Methods: We found 12 phase II or III randomized clinical trials (RCTs) including 8,453 patients with NSCLC by searching Pubmed, Embase, and ClinicalTrials.gov. Risk ratios (RRs) and 95% confidence interval (CI) were used to compare the rate of immune-related adverse events (irAEs) for different ICIs-based treatments using pairwise and network meta-analysis with random effects. Results: For dermatologic irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (97.4%), pembrolizumab (80.1%), nivolumab (67.1%), pembrolizumab + platinum (43.3%), atezolizumab + platinum (39.9%), durvalumab (17.5%), platinum-based chemotherapy (4.7%). For colitis, the corresponding ranking of incidences of the six groups from high to low was: atezolizumab + platinum (77.1%), nivolumab (67.3%), pembrolizumab (60.5%), durvalumab (45.2%), pembrolizumab + platinum (41.4%), platinum-based chemotherapy (8.5%). For endocrine irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (79.1%), durvalumab (69.1%), pembrolizumab (61.9%), atezolizumab + platinum (60.4%),nivolumab (45.7%), pembrolizumab + platinum (33.5%), platinum-based chemotherapy (0.3%). For pneumonitis, the corresponding ranking of incidences of the seven groups from high to low was: pembrolizumab (99.3%), pembrolizumab + platinum (65.1%), durvalumab (62.2%), atezolizumab + platinum (56%), nivolumab (35.9%), platinum-based chemotherapy (18.1%),atezolizumab (13.3%). For hepatitis, the corresponding ranking of incidences of the six groups from high to low was: pembrolizumab (71.2%), pembrolizumab + platinum (64.3%), durvalumab (56.4%), atezolizumab + platinum (53.8%), nivolumab (44.5%), platinum-based chemotherapy (9.8%). Conlusion: In addition to platinum-based chemotherapy, durvalumab for dermatologic and liver irAEs, pembrolizumab for gastrointestinal irAEs, pembrolizumab + platinum for endocrine irAEs, and atezolizumab for pneumonitis may be associated with lower rates of irAEs than other immune-based regimens. Nivolumab + ipilimumab for dermatologic and endocrine irAEs, atezolizumab + platinum for colitis, and pembrolizumab for pneumonitis and hepatitis may be associated with higher rates of irAEs.