A framework for extension studies using real-world data to examine long-term safety and effectiveness

Understanding the long-term benefits and risks of treatments, devices, and vaccines is critically important for individual- and population-level healthcare decision-making. Extension studies, or \u27roll-over studies,\u27 are studies that allow for patients participating in a parent clinical trial to \u27roll-over\u27 into a subsequent related study to continue to observe and measure long-term safety, tolerability, and/or effectiveness. These designs are not new and are often used as an approach to satisfy regulatory post-approval safety requirements. However, designs using traditional clinical trial infrastructure can be expensive and burdensome to conduct, particularly, when following patients for many years post trial completion. Given the increasing availability and access of real-world data (RWD) sources, direct-to-patient technologies, and novel real-world study designs, there are more cost-efficient approaches to conducting extension studies while assessing important long-term outcomes. Here, we describe various fit-for-purpose design options for extension studies, discuss related methodological considerations, and provide scientific and operational guidance on practices when planning to conduct an extension study using RWD. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE)

Evaluación agronómica de la adaptación, producción y reproducción de aloe barbadensis bajo 4 tratamientos y 3 condiciones de cultivo en el municipio de Turbo –Antioquia

NingunoEn la presente investigación se evaluó la capacidad de adaptación, producción y reproducción de Aloe barbadensis bajo 4 tratamientos y 3 condiciones de cultivo en el municipio de Turbo, las plantas empleadas para este estudio fueron traídas desde el municipio de barrancas, la guajira, lugar donde se encuentran cultivos de ella bajo condiciones agroambientales de mayor temperatura, menor humedad y pluviosidad que las condiciones del municipio de Turbo, el objetivo principal de este estudio es establecer nuevas alternativas de producción mediante el uso de tratamientos orgánicos, con la finalidad de mejorar el rendimiento del cultivo. Para llevar a cabo la investigación se establecieron 100 plantas en cada uno de los tratamientos (testigo, bovinaza, cascarilla de arroz y aserrín) y en cada uno de los modelos (sin camellón 34 plantas, con camellón 33 plantas y camellón cubierto 33 plantas), para determinar el crecimiento se contaron las hojas de cada planta cada 15 días en cada tratamiento, el trabajo se realizó mediante el uso de investigación cualitativa para lograr describir el proceso de adaptación de las platas y de investigación cuantitativa para establecer el efecto de los tratamientos a utilizar. Los resultados de la tasa de producción y reproducción de A. Barbadensis no presentaron diferencias estadísticamente significativas (P-valor < 0,05), entre los tratamientos y las condiciones de siembra, a excepción del número de rebrotes por planta, donde se evidenció una interacción menor a 0,05. Por consiguiente, se determinó que, bajo la condición con camellón sin plástico, utilizando los tratamientos cascarilla y aserrín se obtiene un mayor incremento en el número de rebrotes por planta.In the present investigation the capacity of adaptation, production and reproduction of Aloe barbadensis was evaluated under 4 treatments and 3 cultivation conditions in the municipality of Turbo, the plants used for this study were brought from the municipality of canyons, la guajira, where crops are found under agro-environmental conditions of higher temperature, lower humidity and rainfall than the conditions of the municipality of Turbo, the main objective of this study is to establish new production alternatives through the use of organic treatments, in order to improve yield of the crop To carry out the investigation, 100 plants were established in each of the treatments (control, bovinaza, rice husk and sawdust) and in each of the models (without ridge 34 plants, with ridge 33 plants and ridge covered 33 plants) , to determine the growth, the leaves of each plant were counted every 15 days in each treatment, the work was carried out through the use of qualitative research to describe the process of adaptation of the plants and quantitative research to establish the effect of the treatments to use. The results of the production and reproduction rate of A. Barbadensis did not show statistically significant differences (P-value <0.05), between treatments and planting conditions, with the exception of the number of regrowths per plant, where there was evidence of interaction less than 0.05. Therefore, it was determined that, under the condition with a ridge without plastic, using the scale and sawdust treatments, a greater increase in the number of regrowths per plant is obtained

Foetal ultrasound measurement imputations based on growth curves versus multiple imputation chained equation (MICE)

BackgroundUltrasound measures are valuable for epidemiologic studies of risk factors for growth restriction. Longitudinal measurements enable investigation of rates of change and identification of windows where growth is impacted more acutely. However, missing data can be problematic in these studies, limiting sample size, ability to characterise windows of vulnerability, and in some instances creating bias. We sought to compare a parametric linear mixed model (LMM) approach to multiple imputation in this setting with multiple imputation by chained equation (MICE) methodology.MethodsUltrasound scans performed for clinical purposes were abstracted from women in the LIFECODES birth cohort (n = 1003) if they were close in time to three study visits (median 18, 26, and 35 weeks’ gestation). We created imputed datasets using LMM and MICE and calculated associations between demographic factors and ultrasound parameters cross‐sectionally and longitudinally. Results were compared with a complete‐case analysis.ResultsMost participants had ultrasounds at 18 weeks’ gestation, and ~50% had measurements at 26 and 35 weeks; 100% had birthweight. Associations between demographic factors and ultrasound measures were similar in magnitude, but more precise, when either imputed datasets were used, compared with a complete‐case analysis, in both the cross‐sectional or longitudinal analyses.ConclusionsMICE, though ignoring the non‐linear features of the trajectory and within subject correlation, is able to provide reasonable imputation of foetal growth data when compared to LMM. Because it simultaneously imputes missing covariate data and does not require specification of variance structure as in LMM, MICE may be preferable for imputation in this setting.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146300/1/ppe12486_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146300/2/ppe12486.pd

Analysis of correlation of pre-therapeutic assessment and the final diagnosis in endometrial cancer: role of tumor volume in the magnetic resonance imaging

ObjectiveTo evaluate whether the introduction of tumor volume as new parameter in the MRI assessment could improve both concordance between preoperative and postoperative staging, and the identification of histological findings.MethodsA retrospective observational study with 127 patients with endometrial cancer (EC) identified between 2016 and 2021 at the Juan Ramon Jimenez University Hospital, Huelva (Spain) was carried out. Tumor volume was measured in three ways. Analyses of Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) were performed.ResultsAlthough preoperative MRI had an 89.6% and 66.7% sensitivity for the detection of deep mucosal invasion and cervical stroma infiltration, preoperative assessment had an intraclass correlation coefficient of 0.517, underestimating tumor final stage in 12.6% of cases, with a poor agreement between preoperative MRI and postoperative staging (κ=0.082) and low sensitivity (14.3%) for serosa infiltration. The cut-off values for all three volume parameters had good/excellent AUC (0.73-0.85), with high sensitivity (70-83%) and specificity (64-84%) values for all histopathological variables. Excellent/good agreement was found all volume parameters for the identification of deep myometrial invasion (0.71), cervical stroma infiltration (0.80), serosa infiltration (0.81), and lymph node metastases (0.81).ConclusionTumor volume measurements have good predictive capacity to detect histopathological findings that affect final tumor staging and might play a crucial role in the preoperative assessment of patients with endometrial cancer in the future

Study of platelet kinetics in immune thrombocytopenia to predict splenectomy response

Despite the efficacy of splenectomy for chronic immune thrombocytopenia (ITP), its considerable failure rate and its possible related complications prove the need for further research into potential predictors of response. The platelet sequestration site determined by 111In-labelled autologous platelet scintigraphy has been proposed to predict splenectomy outcome, but without standardisation in clinical practice. Here, we conducted a single-centre study by analysing a cohort of splenectomised patients with ITP in whom 111In-scintigraphy was performed at La Paz University Hospital in Madrid to evaluate the predictive value of the platelet kinetic studies. We also studied other factors that could impact the splenectomy outcome, such as patient and platelet characteristics. A total of 51 patients were splenectomised, and 82.3% responded. The splenic sequestration pattern predicted a higher rate of complete response up to 12 months after splenectomy (p = 0.005), with 90% sensitivity and 77% specificity. Neither age, comorbidities, therapy lines nor previous response to them showed any association with response. Results from the platelet characteristics analysis revealed a significant loss of sialic acid in platelets from the non-responding patients compared with those who maintained a response (p = 0.0017). Our findings highlight the value of splenic sequestration as an independent predictor of splenectomy respons

The importance of platelet glycoside residues in the haemostasis of patients with immune thrombocytopaenia

Loss of sialic acid from the carbohydrate side chains of platelet glycoproteins can affect platelet clearance, a proposed mechanism involved in the etiopathogenesis of immune thrombocy-topaenia (ITP). We aimed to assess whether changes in platelet glycosylation in patients with ITP affected platelet counts, function, and apoptosis. This observational, prospective, and transversal study included 82 patients with chronic primary ITP and 115 healthy controls. We measured platelet activation markers and assayed platelet glycosylation and caspase activity, analysing samples using flow cytometry. Platelets from patients with ITP with a platelet count &lt;30 × 103/µL presented less sialic acid. Levels of α1,6-fucose (a glycan residue that can directly regulate antibody-dependent cellular cytotoxicity) and α-mannose (which can be recognised by mannose-binding-lectin and acti-vate the complement pathway) were increased in the platelets from these patients. Platelet surface exposure of other glycoside residues due to sialic acid loss inversely correlated with platelet count and the ability to be activated. Moreover, loss of sialic acid induced the ingestion of platelets by human hepatome HepG2 cells. Changes in glycoside composition of glycoproteins on the platelets’ surface impaired their functional capacity and increased their apoptosis. These changes in platelet glycoside residues appeared to be related to ITP severity.This research was funded by FIS-Fondos FEDER PI19/00631, FIS-Fondos FEDER PI19/00772 and Platelet Disorder Support Associatio

Pacientes Nao Responsivos à Terapia de Ressincronizaçao Cardíaca

Em que pesem os avanços científicos e o aumento do número de implantes de ressincronizadores cardíacos, a porcentagem de pacientes nao responsivos varia de 11 a 43%, na dependência dos critérios utilizados. Este artigo faz uma revisao das causas associadas à ausência de resposta efetiva à terapia de ressincronizaçao cardíaca (TRC), assim como dos cuidados para reduzir o número de pacientes nao responsivos. Essas medidas incluem critérios de seleçao adequados dos candidatos à TRC, cuidados durante o implante e otimizaçao da programaçao dos dispositivos durante o acompanhamento dos pacientes

Pacientes Nao Responsivos à Terapia de Ressincronizaçao Cardíaca

Em que pesem os avanços científicos e o aumento do número de implantes de ressincronizadores cardíacos, a porcentagem de pacientes nao responsivos varia de 11 a 43%, na dependência dos critérios utilizados. Este artigo faz uma revisao das causas associadas à ausência de resposta efetiva à terapia de ressincronizaçao cardíaca (TRC), assim como dos cuidados para reduzir o número de pacientes nao responsivos. Essas medidas incluem critérios de seleçao adequados dos candidatos à TRC, cuidados durante o implante e otimizaçao da programaçao dos dispositivos durante o acompanhamento dos pacientes

Pacientes Nao Responsivos à Terapia de Ressincronizaçao Cardíaca

Em que pesem os avanços científicos e o aumento do número de implantes de ressincronizadores cardíacos, a porcentagem de pacientes nao responsivos varia de 11 a 43%, na dependência dos critérios utilizados. Este artigo faz uma revisao das causas associadas à ausência de resposta efetiva à terapia de ressincronizaçao cardíaca (TRC), assim como dos cuidados para reduzir o número de pacientes nao responsivos. Essas medidas incluem critérios de seleçao adequados dos candidatos à TRC, cuidados durante o implante e otimizaçao da programaçao dos dispositivos durante o acompanhamento dos pacientes