78 research outputs found
Patient values in patient-provider communication about participation in early phase clinical cancer trials:a qualitative analysis before and after implementation of an online value clarification tool intervention
Background: Patients with advanced cancer who no longer have standard treatment options available may decide to participate in early phase clinical trials (i.e. experimental treatments with uncertain outcomes). Shared decision-making (SDM) models help to understand considerations that influence patients’ decision. Discussion of patient values is essential to SDM, but such communication is often limited in this context and may require new interventions. The OnVaCT intervention, consisting of a preparatory online value clarification tool (OnVaCT) for patients and communication training for oncologists, was previously developed to support SDM. This study aimed to qualitatively explore associations between patient values that are discussed between patients and oncologists during consultations about potential participation in early phase clinical trials before and after implementation of the OnVaCT intervention. Methods: This study is part of a prospective multicentre nonrandomized controlled clinical trial and had a between-subjects design: pre-intervention patients received usual care, while post-intervention patients additionally received the OnVaCT. Oncologists participated in the communication training between study phases. Patients’ initial consultation on potential early phase clinical trial participation was recorded and transcribed verbatim. Applying a directed approach, two independent coders analysed the transcripts using an initial codebook based on previous studies. Steps of continuous evaluation and revision were repeated until data saturation was reached. Results: Data saturation was reached after 32 patient-oncologist consultations (i.e. 17 pre-intervention and 15 post-intervention). The analysis revealed the values: hope, perseverance, quality or quantity of life, risk tolerance, trust in the healthcare system/professionals, autonomy, social adherence, altruism, corporeality, acceptance of one’s fate, and humanity. Patients in the pre-intervention phase tended to express values briefly and spontaneously. Oncologists acknowledged the importance of patients’ values, but generally only gave ‘contrasting’ examples of why some accept and others refuse to participate in trials. In the post-intervention phase, many oncologists referred to the OnVaCT and/or asked follow-up questions, while patients used longer phrases that combined multiple values, sometimes clearly indicating their weighing. Conclusions: While all values were recognized in both study phases, our results have highlighted the different communication patterns around patient values in SDM for potential early phase clinical trial participation before and after implementation of the OnVaCT intervention. This study therefore provides a first (qualitative) indication that the OnVaCT intervention may support patients and oncologists in discussing their values. Trial registration: Netherlands Trial Registry: NL7335, registered on July 17, 2018.</p
Patient values in patient-provider communication about participation in early phase clinical cancer trials:a qualitative analysis before and after implementation of an online value clarification tool intervention
Background: Patients with advanced cancer who no longer have standard treatment options available may decide to participate in early phase clinical trials (i.e. experimental treatments with uncertain outcomes). Shared decision-making (SDM) models help to understand considerations that influence patients’ decision. Discussion of patient values is essential to SDM, but such communication is often limited in this context and may require new interventions. The OnVaCT intervention, consisting of a preparatory online value clarification tool (OnVaCT) for patients and communication training for oncologists, was previously developed to support SDM. This study aimed to qualitatively explore associations between patient values that are discussed between patients and oncologists during consultations about potential participation in early phase clinical trials before and after implementation of the OnVaCT intervention. Methods: This study is part of a prospective multicentre nonrandomized controlled clinical trial and had a between-subjects design: pre-intervention patients received usual care, while post-intervention patients additionally received the OnVaCT. Oncologists participated in the communication training between study phases. Patients’ initial consultation on potential early phase clinical trial participation was recorded and transcribed verbatim. Applying a directed approach, two independent coders analysed the transcripts using an initial codebook based on previous studies. Steps of continuous evaluation and revision were repeated until data saturation was reached. Results: Data saturation was reached after 32 patient-oncologist consultations (i.e. 17 pre-intervention and 15 post-intervention). The analysis revealed the values: hope, perseverance, quality or quantity of life, risk tolerance, trust in the healthcare system/professionals, autonomy, social adherence, altruism, corporeality, acceptance of one’s fate, and humanity. Patients in the pre-intervention phase tended to express values briefly and spontaneously. Oncologists acknowledged the importance of patients’ values, but generally only gave ‘contrasting’ examples of why some accept and others refuse to participate in trials. In the post-intervention phase, many oncologists referred to the OnVaCT and/or asked follow-up questions, while patients used longer phrases that combined multiple values, sometimes clearly indicating their weighing. Conclusions: While all values were recognized in both study phases, our results have highlighted the different communication patterns around patient values in SDM for potential early phase clinical trial participation before and after implementation of the OnVaCT intervention. This study therefore provides a first (qualitative) indication that the OnVaCT intervention may support patients and oncologists in discussing their values. Trial registration: Netherlands Trial Registry: NL7335, registered on July 17, 2018.</p
Characterization of novel components of the baculovirus per os infectivity factor complex
Baculovirus occlusion-derived virus (ODV) infects insect midgut cells under alkaline conditions, a process mediated by highly conserved per os infectivity factors (PIFs), P74 (PIF0), PIF1, PIF2, PIF3, PIF4, and PIF5 (ODV-E56). Previously, a multimolecular complex composed of PIF1, PIF2, PIF3, and P74 was identified which was proposed to play an essential role during ODV entry. Recently, more proteins have been identified that play important roles in ODV oral infectivity, including PIF4, PIF5, and SF58, which might work in concert with previously known PIFs to facilitate ODV infection. In order to understand the ODV entry mechanism, the identification of all components of the PIF complex is crucial. Hence, the aim of this study was to identify additional components of the PIF complex. Coimmunoprecipitation (CoIP) combined with proteomic analysis was used to identify the components of the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) PIF complex. PIF4 and P95 (AC83) were identified as components of the PIF complex while PIF5 was not, and this was confirmed with blue native PAGE and a second CoIP. Deletion of the pif4 gene impaired complex formation, but deletion of pif5 did not. Differentially denaturing SDS-PAGE further revealed that PIF4 forms a stable complex with PIF1, PIF2, and PIF3. P95 and P74 are more loosely associated with this complex. Three other proteins, AC5, AC68, and AC108 (homologue of SF58), were also found by the proteomic analysis to be associated with the PIF complex. Finally the functional significance of the PIF protein interactions is discussed
Decisional Conflict after Deciding on Potential Participation in Early Phase Clinical Cancer Trials:Dependent on Global Health Status, Satisfaction with Communication, and Timing
SIMPLE SUMMARY: Early phase clinical trials are an essential part of modern drug development and thus the advance of anti-cancer therapies for patients. However, deciding whether to participate in such trials can be complex and patients have reported decisional conflict (i.e., unresolved decisional needs). The aim of our study was to untangle several factors that contribute to decisional conflict in patients with advanced cancer who have recently been asked to decide whether to participate in early phase clinical trials. We found that patients experienced less decisional conflict if they had a better global health status, higher satisfaction, and made their decision sooner. Other factors, such as the decision to (not) participate, did not prove to be the best indicators for decisional conflict. With these insights, we can start to build hypotheses on how to improve the decision-making process for patients with end-stage cancer, which can ultimately improve their quality of life. ABSTRACT: When standard treatment options are not available anymore, patients with advanced cancer may participate in early phase clinical trials. Improving this complex decision-making process may improve their quality of life. Therefore, this prospective multicenter study with questionnaires untangles several contributing factors to decisional conflict (which reflects the quality of decision-making) in patients with advanced cancer who recently decided upon early phase clinical trial participation (phase I or I/II). We hypothesized that health-related quality of life, health literacy, sense of hope, satisfaction with the consultation, timing of the decision, and the decision explain decisional conflict. Mean decisional conflict in 116 patients was 30.0 (SD = 16.9). Multivariate regression analysis showed that less decisional conflict was reported by patients with better global health status (β = −0.185, p = 0.018), higher satisfaction (β = −0.246, p = 0.002), and who made the decision before (β = −0.543, p < 0.001) or within a week after the consultation (β = −0.427, p < 0.001). These variables explained 37% of the variance in decisional conflict. Healthcare professionals should realize that patients with lower global health status and who need more time to decide may require additional support. Although altering such patient intrinsic characteristics is difficult, oncologists can impact the satisfaction with the consultation. Future research should verify whether effective patient-centered communication could prevent decisional conflict
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program
The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits
An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis
Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D
Checklist dos percevejos-do-mato (Hemiptera: Heteroptera: Pentatomoidea) do Estado de São Paulo, Brasil
The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care
Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system
- …