RESUMEN
Water pollution is an inextricable problem that stems from natural and human-related factors. Unfortunately, with rapid industrialization, the problem has escalated to alarming levels. The pollutants that contribute to water pollution include heavy metals (HMs), chemicals, pesticides, pharmaceuticals, and other industrial byproducts. Numerous methods are used for treating HMs in wastewater, like ion exchange, membrane filtration, chemical precipitation, adsorption, and electrochemical treatment. But the remediation through the plant, i.e., phytoremediation is the most sustainable approach to remove the contaminants from wastewater. Aquatic plants illustrate the capacity to absorb excess pollutants including organic and inorganic compounds, HMs, and pharmaceutical residues present in agricultural, residential, and industrial discharges. The extensive exploitation of these hyperaccumulator plants can be attributed to their abundance, invasive mechanisms, potential for bioaccumulation, and biomass production. Post-phytoremediation, plant biomass can be toxic to both water bodies and soil. Therefore, the circular bioeconomy approach can be applied to reuse and repurpose the toxic plant biomass into different circular bioeconomy byproducts such as biochar, biogas, bioethanol, and biodiesel is essential. In this regard, the current review highlights the potential strategies for the phytoremediation of HMs in wastewater and various strategies to efficiently reuse metal-enriched biomass material and produce commercially valuable products. The implementation of circular bioeconomy practices can help overcome significant obstacles and build a new platform for an eco-friendlier lifestyle.
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Biodegradación Ambiental , Metales Pesados , Aguas Residuales , Contaminantes Químicos del Agua , Metales Pesados/metabolismo , Metales Pesados/análisis , Aguas Residuales/química , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Eliminación de Residuos Líquidos/métodos , Plantas/metabolismoRESUMEN
OBJECTIVES: Survival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared. METHODS: Three different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates. RESULTS: Standard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model). CONCLUSIONS: Where a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas.
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Receptores Quiméricos de Antígenos , Antígenos CD19/uso terapéutico , Tratamiento Basado en Trasplante de Células y Tejidos , Estudios de Seguimiento , Humanos , Inmunoterapia Adoptiva , Recurrencia Local de NeoplasiaRESUMEN
ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 106 CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.
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Corticoesteroides/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso/terapia , Corticoesteroides/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/efectos adversos , Productos Biológicos/efectos adversos , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Femenino , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Masculino , Persona de Mediana EdadAsunto(s)
Productos Biológicos/administración & dosificación , Linfoma de Células B Grandes Difuso , Proteínas de Neoplasias/inmunología , Escape del Tumor/efectos de los fármacos , Adulto , Antígenos CD19/inmunología , Productos Biológicos/efectos adversos , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia , Escape del Tumor/genéticaRESUMEN
BACKGROUND: Several mapping algorithms have been published with the EORTC-QLQ-C30 for estimating EQ-5D-3L utilities. However, none are available with EQ-5D-5L. Moreover, a comparison between mapping algorithms in the same set of patients has not been performed for these two instruments simultaneously. In this prospective data set of 100 non-small cell lung cancer (NSCLC) patients, we investigate three mapping algorithms using the EQ-5D-3L and EQ-5D-5L and compare their performance. METHODS: A prospective non-interventional cohort of 100 NSCLC patients were followed up for 12 months. EQ-5D-3L, EQ-5D-5L and EORTC-QLQ-C30 were assessed monthly. EQ-5D-5L was completed at least 1 week after EQ-5D-3L. A random effects linear regression model, a beta-binomial (BB) and a Limited Variable Dependent Mixture (LVDM) model were used to determine a mapping algorithm between EQ-5D-3L, EQ-5D-5L and QLQ-C30. Simulation and cross validation and other statistical measures were used to compare the performances of the algorithms. RESULTS: Mapping from the EQ-5D-5L was better: lower AIC, RMSE, MAE and higher R(2) were reported with the EQ-5D-5L than with EQ-5D-3L regardless of the functional form of the algorithm. The BB model proved to be more useful for both instruments: for the EQ-5D-5L, AIC was -485, R(2) of 75 %, MAE of 0.075 and RMSE was 0.092. This was -385, 69 %, 0.099 and 0.113 for EQ-5D-3L respectively. The mean observed vs. predicted utilities were 0.572 vs. 0.577 and 0.515 vs. 0.523 for EQ-5D-5L and EQ-5D-3L respectively, for OLS; for BB, these were 0.572 vs. 0.575 and 0.515 vs. 0.518 respectively and for LVDMM 0.532 vs 0.515 and 0.569 vs 0.572 respectively. Less over-prediction at poorer health states was observed with EQ-5D-5L. CONCLUSIONS: The BB mapping algorithm is confirmed to offer a better fit for both EQ-5D-3L and EQ-5D-5L. The results confirm previous and more recent results on the use of BB type modelling approaches for mapping. It is recommended that in studies where EQ-5D utilities have not been collected, an EQ-5D-5L mapping algorithm is used.
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Algoritmos , Carcinoma de Pulmón de Células no Pequeñas/psicología , Calidad de Vida/psicología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Modelos Teóricos , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: The EORTC-QLQ-C30 is a widely used health related quality of life (HRQoL) questionnaire in lung cancer patients. Small HRQoL treatment effects are often reported as mean differences (MDs) between treatments, which are rarely justified or understood by patients and clinicians. An alternative approach using odds ratios (OR) for reporting effects is proposed. This may offer advantages including facilitating alignment between patient and clinician understanding of HRQoL effects. METHODS: Data from six CRUK sponsored randomized controlled lung cancer trials (2 small cell and 4 in non-small cell, in 2909 patients) were used to HRQoL effects. Results from Beta-Binomial (BB) standard mixed effects were compared. Preferences for ORs vs MDs were determined and Time to Deterioration (TD) was also compared. RESULTS: HRQoL effects using ORs offered coherent interpretations: MDs >0 resulted in ORs >1 and vice versa; effect sizes were classified as 'Trivial' if the OR was between 1 ± 0.05 (i.e. 0.95 to 1.05); 'Small': for 1 ± 0.1; 'Medium': 1 ± 0.2 and 'Large': OR <0.8 or >1.20. Small HRQoL effects on the MD scale may translate to important treatment differences on the OR scale: for example, a worsening in symptoms (MD) by 2.6 points (p = 0.1314) would be a 17 % deterioration (p < 0.0001) with an OR. Hence important differences may be missed with MD; conversely, small ORs are unlikely to yield large MDs because methods based on OR model skewed data well. Initial evidence also suggests oncologists prefer ORs over MDs since interpretation is similar to hazard ratios. CONCLUSION: Reporting HRQoL benefits as MDs can be misleading. Estimates of HRQoL treatment effects in terms of ORs are preferred over MDs. Future analysis of QLQ-C30 and other HRQoL measures should consider reporting HRQoL treatment effects as ORs.
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Neoplasias Pulmonares/terapia , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Extraction of coal through opencast mining leads to the buildup of heaps of overburden (OB) material, which poses a significant risk to production safety and environmental stability. A systematic bibliometric analysis to identify research trends and gaps, and evaluate the impact of studies and authors in the field related to coal OB phytostabilization was conducted. Key issues associated with coal extraction include land degradation, surface and groundwater contamination, slope instability, erosion and biodiversity loss. Handling coal OB material intensifies such issues, initiating additional environmental and physical challenges. The conventional approach such as topsoiling for OB restoration fails to restore essential soil properties crucial for sustainable vegetation cover. Phytostabilization approach involves establishing a self-sustaining plant cover over OB dump surfaces emerges as a viable strategy for OB restoration. This method enhanced by the supplement of organic amendments boosts the restoration of OB dumps by improving rhizosphere properties conducive to plant growth and contaminant uptake. Criteria essential for plant selection in phytostabilization are critically evaluated. Native plant species adapted to local climatic and ecological conditions are identified as key agents in stabilizing contaminants, reducing soil erosion, and enhancing ecosystem functions. Applicable case studies of successful phytostabilization of coal mines using native plants, offering practical recommendations for species selection in coal mine reclamation projects are provided. This review contributes to sustainable approaches for mitigating the environmental consequences of coal mining and facilitates the ecological recovery of degraded landscapes.
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The study explores the causal relationship between monetary policy effectiveness and financial inclusion in developed and under-developed countries. Structural Vector Auto-regressive techniques have been inducted to explore the relationship between monetary policy effectiveness and financial inclusion. The study covers the secondary data of 10 developed and 30 underdeveloped countries throughout 2004-2018. It is concluded that monetary policy effectiveness and financial inclusion do not have a contemporaneous impact on each other. Nevertheless, the reduced-form Vector Auto-regressive witness the reverse causality between financial inclusion and monetary policy effectiveness in developed countries. Thus, effective monetary policy enhances financial inclusion in a country, and a higher degree of financial inclusion lowers the inflation rate and makes monetary policy effective. One way causality from monetary policy effectiveness to financial inclusion can be observed in under-developed countries. Using the Structural Vector auto-regressive technique and financial inclusion index composed of three-dimension to examine the relationship of monetary policy effectiveness and financial inclusion in developed and developing countries is considered the study's significant contribution.
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Países en Desarrollo/economía , Desarrollo Económico , Desarrollo Sostenible/economía , Humanos , Inflación Económica , Modelos Económicos , Pobreza/economíaRESUMEN
BACKGROUND: Bevacizumab is an antiangiogenic recombinant humanized monoclonal antibody that inhibits tumor growth. FKB238, a bevacizumab biosimilar, has analytical pharmacokinetic and safety profiles similar to those of bevacizumab. OBJECTIVE: This phase III trial (NCT02810457) compared the efficacy and safety of FKB238 with that of bevacizumab in patients with advanced/recurrent non-squamous non-small-cell lung cancer (non-sq-NSCLC). METHODS: This global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized patients with advanced/recurrent non-sq-NSCLC to receive intravenous infusions of either FKB238 15 mg/kg or bevacizumab 15 mg/kg. All patients received intravenous infusions of paclitaxel 200 mg/m2 and carboplatin (area under the curve 6.0) immediately prior to investigational products for 4-6 cycles. FKB238 and bevacizumab were administered on day 1 of each 21-day cycle until objective progressive disease by RECIST version 1.1 or other discontinuation criteria were met. The primary efficacy endpoint was overall response rate (ORR), including complete and partial response and based on blinded independent central review assessment. Other efficacy determinations included progression-free survival (PFS), overall survival (OS), and immunogenicity. Adverse events and severity were reported. RESULTS: The ORR for the intent-to-treat (ITT) population (N = 731) was 51.6% in the FKB238 arm (N = 364) and 53.7% in the bevacizumab arm (N = 367). The FKB238:bevacizumab ORR ratio (ITT population) was 0.96 (90% confidence interval [CI] 0.86-1.08), and the difference in ORR (per-protocol set) between FKB238 and bevacizumab was - 0.02 (95% CI - 0.09 to 0.06). Both CIs fell within the prespecified equivalence margins. Estimated median PFS was 7.72 and 7.62 months in the FKB238 and bevacizumab arms, respectively (hazard ratio 0.97; 95% CI 0.82-1.16). Treatment-emergent adverse events (TEAEs) were reported for 94.2% and 95.1% of patients in the FKB238 and bevacizumab arms, respectively. Grade 3 or higher TEAEs were reported for 53.6% and 55.5% of patients in the FKB238 and bevacizumab arms, respectively. Serious TEAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and bevacizumab, respectively. CONCLUSIONS: Efficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC. TRIAL REGISTRATION NUMBER: NCT02810457.
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Biosimilares Farmacéuticos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Biosimilares Farmacéuticos/efectos adversos , Carboplatino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel , Resultado del TratamientoRESUMEN
BACKGROUND: To undertake a systematic review of the available data for oral and intravenous topotecan in adults with relapsed small cell lung cancer (SCLC) for whom re-treatment with the first line regimen is not considered appropriate. METHODS: We searched six databases from 1980 up to March 2009 for relevant trials regardless of language or publication status. Relevant studies included any randomised trial of any chemotherapeutic treatment against any comparator in this licensed indication. Where possible we used opposite quantitative methods. Where meta-analysis was considered unsuitable for some or all of the data, we employed a narrative synthesis method. For indirect comparisons we used the method of Bucher et al., where available data allowed it, otherwise we used narrative descriptions. RESULTS: Seven unique studies met the inclusion criteria, four of which could be used in our analyses. These included one study comparing oral topotecan plus best supportive care (BSC) to BSC alone, one study comparing intravenous topotecan to cyclophosphamide, adriamycin and vincristine (CAV), and two studies comparing oral topotecan with intravenous topotecan. All four studies appear to be well conducted and with low risk of bias. Oral topotecan plus BSC has advantages over BSC alone in terms of survival (hazard ratio = 0.61; 95% CI, 0.43 to 0.87) and quality of life (EQ-5 D difference: 0.15; 95% CI, 0.05 to 0.25). Intravenous topotecan was at least as effective as CAV in the treatment of patients with recurrent small-cell lung cancer and resulted in improved quality-of-life with respect to several symptoms. CAV was associated with significantly less grade 4 thrombocytopenia compared with IV topotecan (risk ratio = 5.83; 95% CI, 2.35 to 14.42). Survival (hazard ratio = 0.98; 95% CI, 0.77 to 1.25) and response (pooled risk ratio = 1.04; 95% CI, 0.58 to 1.85) data were similar for the oral and IV topotecan groups. Symptom control was also very similar between the trials and between the oral and IV groups. Toxicity data showed a significant difference in favour of oral topotecan for neutropenia (pooled risk ratio = 0.65; 95% CI, 0.47 to 0.89). Indirect evidence showed that oral topotecan was at least as good as or better than CAV on all outcomes (survival, response rates, toxicities, and symptoms) that allowed indirect comparisons, with the only exception being grade four thrombocytopenia which occurred less often on CAV treatment. CONCLUSIONS: Concerning topotecan both the oral and intravenous options have similar efficacy, and patient preference may be a decisive factor if the choice would be between the two formulations. The best trial evidence for decision making, because it was tested versus best supportive care, exists for oral topotecan. Indirectly, because we have two head-to-head comparisons of oral versus intravenous topotecan, and one comparison of intravenous topotecan versus CAV in similar patients as in the trial against best supportive care, one might infer that IV topotecan and CAV could also be superior to best supportive care, and that oral topotecan has similar effects to CAV with possibly better symptom control. From the evidence discussed above, it is evident that oral topotecan has similar efficacy to IV topotecan (direct comparison) and CAV (indirect comparison). There is no further evidence base of direct or possible indirect comparisons for other comparators than CAV of either oral or IV topotecan.
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Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Inhibidores de Topoisomerasa/uso terapéutico , Topotecan/uso terapéutico , Humanos , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
Congenital diaphragmatic hernia is a congenital defect of the diaphragm through which intestine and other viscera herniate into the chest. In extreme form of diaphragmatic maldevelopment, there might be a complete agenesis of diaphragm. A 45-day old male infant was presented with fever, cough and respiratory distress for a week. Chest radiograph showed right-sided congenital diaphragmatic hernia. The patient underwent surgical exploration and found to have an unusual and large defect of right hemidiaphragm. The diaphragm was absent on anterior and lateral aspects of the chest wall and only a small rim of diaphragm was present on posterior aspect. The defect was identified as agenesis of right hemidiaphragm and successfully managed by suturing the posterior rim of diaphragm to the intercostal muscles and ribs. This report describes successful management of hemidiaphragmatic agenesis without incorporating a prosthetic material.
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Colonic atresias are the rare malformations of the colon and constitute about 1.7 to 15% of all gastrointestinal (GI) atresias. A 6-month old infant presented with recurrent episodes of sub-acute intestinal obstruction since birth. During the index admission, patient had clinical signs of complete intestinal obstruction. The patient was operated and type I sigmoid-colon atresia found which on further exploration tuned out to be of perforated mucosal web variety. The resection of the involved part of colon and a primary end to oblique colo-colic anastomosis was performed.