Aim
A systematic literature review of immuno-oncology trials was conducted to assess the potential impact of open-label vs double-blind trial design on patient-reported outcome (PRO) data.
Methods
A ...systematic search of indexed literature published from January 2009 to May 2019 was conducted using PubMed/MEDLINE, Cochrane Library, and EMBASE database. All randomized clinical trials (RCTs) of immuno-oncology therapies on advanced cancer patients reporting PRO data were identified. Descriptive analyses were performed to quantify differences at baseline and over time, by the type of study, regarding questionnaire completion rate and PRO scores.
Results
In total, 23 studies were retained (15 open-label, 8 blinded). At baseline, no difference in completion rate was observed between arms irrespective of trial design (absolute mean difference of 2.8% and 2.2% for open label and blinded studies, respectively). No clinically significant difference in baseline PRO scores was observed between arms. Over time, impact on PRO scores could not be identified due to the limited number of studies, heterogeneity of questionnaires and tumor types.
Conclusions
Trial design had no impact on PRO completion rate or baseline scores. Future research should involve analyses by specific cancer types and ideally compare individual data from two similar RCTs (blinded vs. open-label).
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CEKLJ, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
New cancer treatments, such as immune checkpoint inhibitors (ICIs), can improve survival and health-related quality of life (HRQoL) in patients with cancer. Although long-term monitoring of HRQoL has ...been shown to improve survival, integration of HRQoL into everyday practice remains poorly documented.
This study describes experiences and expectations of patients treated with ICIs regarding a discussion of HRQoL with health care professionals (HCPs) in cancer management.
This cross-sectional study was conducted in an online patient community (Carenity) in France. Patients treated with ICIs for cancer, included between September 2018 and January 2019, completed a questionnaire to assess the involvement of HCP in a discussion of HRQoL and when and what was discussed.
Of 82 patients included (mean age: 56.9 years, 95% CI 54.2-59.6; 46 56% male; 34 41% with lung cancer), 62 (76%) reported discussing HRQoL at least once with HCPs, mainly general practitioners (54/82, 66%), oncologists (53/82, 65%), and hospital nurses (50/82, 61%). Around half (45/82, 55%) of the patients were satisfied with these discussions. Discussions with the oncologist were at the patient's initiative (34/53, 64%). Discussions occurred primarily during follow-up visits (40/62, 65%), when adverse events occurred (30/62, 48%), and at treatment initiation (27/62, 32%). The most discussed dimensions were symptoms (48/62, 77%) and physical well-being (43/62, 69%). With respect to expectations, 54/82 (66%) patients considered oncologists as the most important HCPs for discussing HRQoL. These discussions were desirable throughout the care pathway, particularly at diagnosis (63/82, 77%) and when treatment was initiated (75/82, 92%) or changed (68/82, 83%). All HRQoL dimensions were considered important to discuss.
With only around half of the patients satisfied with HRQoL discussions, impactful HRQoL integration in clinical practice is critical. According to patients, this integration should involve mainly oncologists and general practitioners, should happen at every step of the care pathway, and should be extended to dimensions that are currently rarely addressed.
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Immune checkpoint inhibitors (ICIs) are increasingly used to treat several types of tumors. Impact of this emerging therapy on patients' health-related quality of life (HRQoL) is usually collected in ...clinical trials through standard questionnaires. However, this might not fully reflect HRQoL of patients under real-world conditions. In parallel, users' narratives from social media represent a potential new source of research concerning HRQoL.
The aim of this study is to assess and compare coverage of ICI-treated patients' HRQoL domains and subdomains in standard questionnaires from clinical trials and in real-world setting from social media posts.
A retrospective study was carried out by collecting social media posts in French language written by internet users mentioning their experiences with ICIs between January 2011 and August 2018. Automatic and manual extractions were implemented to create a corpus where domains and subdomains of HRQoL were classified. These annotations were compared with domains covered by 2 standard HRQoL questionnaires, the EORTC QLQ-C30 and the FACT-G.
We identified 150 users who described their own experience with ICI (89/150, 59.3%) or that of their relative (61/150, 40.7%), with 137 users (91.3%) reporting at least one HRQoL domain in their social media posts. A total of 8 domains and 42 subdomains of HRQoL were identified: Global health (1 subdomain; 115 patients), Symptoms (13; 76), Emotional state (10; 49), Role (7; 22), Physical activity (4; 13), Professional situation (3; 9), Cognitive state (2; 2), and Social state (2; 2). The QLQ-C30 showed a wider global coverage of social media HRQoL subdomains than the FACT-G, 45% (19/42) and 29% (12/42), respectively. For both QLQ-C30 and FACT-G questionnaires, coverage rates were particularly suboptimal for Symptoms (68/123, 55.3% and 72/123, 58.5%, respectively), Emotional state (7/49, 14% and 24/49, 49%, respectively), and Role (17/22, 77% and 15/22, 68%, respectively).
Many patients with cancer are using social media to share their experiences with immunotherapy. Collecting and analyzing their spontaneous narratives are helpful to capture and understand their HRQoL in real-world setting. New measures of HRQoL are needed to provide more in-depth evaluation of Symptoms, Emotional state, and Role among patients with cancer treated with immunotherapy.
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Evaluation of a workplace health promotion program Forette, Françoise; Brieu, Marie-Anne; Lemasson, Hervé ...
Santé publique (Vandoeuvre-lès-Nancy, France),
2014 Jul-Aug, 20140701, Volume:
26, Issue:
4
Journal Article
Peer reviewed
Some studies suggest that a workplace prevention programme could reduce health inequalities related to education level and improve the health status of the employees. The objective of the study was ...to demonstrate the advantages for a company to implement a health prevention programme in the workplace in order to: 1-improve health literacy 2 - change health-related behaviours 3-improve the company image.
A "before - after" methodology was used in a population of 2153 employees of three companies. Three areas of prevention were considered: nutrition, physical activity and prevention of back pain. The successive steps of the EBS programme included general communication, group workshops and individual coaching. Data collection was carried out using anonymous questionnaires sent by e-mail. A global assessment was performed based on the companies' pooled data, with separate analysis according to the steps of the programme.
The programme mobilized employees with participation rates ranging from 25% to 45.5%. After completion of the full programme, 77.5% of respondents reported an improvement of their health knowledge versus 50.3% of those who only received general communication. Behavioural modification was observed, especially in the fields of nutrition and back pain.. EBS can be considered to be a vector of the company image for almost 7 out of 10 employees.
A health prevention education programme provided by the company in the workplace mobilizes employees and contributes to improvement of health knowledge and behaviour change. All approaches tested were important and applicable to various types of companies or workers.
// ABSTRACT IN ENGLISH: Objective: Some studies suggest that a workplace prevention programme could reduce health inequalities related to education level and improve the health status of employees. ...The objective of the study was to demonstrate the advantages for a company to implement a health prevention programme in the workplace in order to: 1 - improve health literacy 2 - change health-related behaviours 3 - improve the company image. Methods: A "before-after" methodology was used in a population of 2153 employees of three companies. Three areas of prevention were considered: nutrition, physical activity and prevention of back pain. The successive steps of the EBS programme included general communication, group workshops and individual coaching. Data collection was carried out using anonymous questionnaires sent by e-mail. A global assessment was performed based on the companies' pooled data, with separate analysis according to the steps of the programme. Results: The programme mobilized employees with participation rates ranging from 25% to 45.5%. After completion of the full programme, 77.5% of respondents reported an improvement of their health knowledge versus 50.3% of those who only received general communication. Behavioural modification was observed, especially in the fields of nutrition and back pain. EBS can be considered to be a vector of the company image for almost seven out of ten employees. Conclusion: A health prevention education programme provided by the company in the workplace mobilizes employees and contributes to improvement of health knowledge and behaviour change. All approaches tested were important and applicable to various types of companies or workers. // ABSTRACT IN FRENCH: Introduction: Un certain nombre de travaux suggèrent que les programmes de prévention réalisés sur le lieu de travail permettent de corriger, en partie, les inégalités liées au niveau d'éducation, améliorent le contrôle des facteurs de risque et apportent des bénéfices en termes de santé. L'objectif de l'étude «Entreprise en Bonne Santé» (EBS) est de démontrer l'intérêt pour une entreprise d'offrir un programme de prévention en santé, sur le lieu et le temps de travail afin: 1 - d'améliorer la culture sanitaire, 2 - de modifier les comportements, 3 - d'améliorer l'image de l'entreprise. Reproduced by permission of Bibliothèque de Sciences Po
Introduction : Un certain nombre de travaux suggèrent que les programmes de prévention réalisés sur le lieu de travail permettent de corriger, en partie, les inégalités liées au niveau d’éducation, ...améliorent le contrôle des facteurs de risque et apportent des bénéfices en termes de santé.L’objectif de l’étude « Entreprise en Bonne Santé » (EBS) est de démontrer l’intérêt pour une entreprise d’offrir un programme de prévention en santé, sur le lieu et le temps de travail afin : 1 – d’améliorer la culture sanitaire, 2 – de modifier les comportements, 3 – d’améliorer l’image de l’entreprise. Méthodes : La méthodologie était de type « avant-après » dans une population de 2 153 personnes de trois entreprises françaises du secteur tertiaire. Trois domaines de prévention ont été abordés : la nutrition, l’activité physique et la prévention du mal de dos. Les étapes successives du programme EBS comprenaient une communication générale, des ateliers de groupes et un coaching individuel. Le recueil des données a été réalisé à l’aide de questionnaires anonymes diffusés par message électronique. Une évaluation globale a été réalisée à partir des données « poolées » des entreprises avec des analyses séparées selon les étapes du programme. Résultats : Le programme a pu mobiliser les collaborateurs des trois entreprises avec un taux de participation au programme complet compris entre 25 % et 45,5 %. Après le programme complet, 77,5 % des répondants ont déclaré avoir amélioré leur culture sanitaire versus 50,3 % de ceux n’ayant bénéficié que de la seule communication générale. Des changements de comportement ont été déclarés, particulièrement dans le domaine de la nutrition et du mal de dos. Enfin, EBS peut être considéré comme un vecteur d’image positive de l’entreprise pour sept salariés sur dix. Conclusion : Un programme de sensibilisation à la prévention santé offert par l’entreprise sur le lieu de travail a largement satisfait les employés et contribue à l’amélioration des connaissances en santé et au changement des comportements. Toutes les approches testées sont importantes et applicables à différents types d’entreprises ou populations.
A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an l-AP4-derived fragment that mimics glutamate and a chain ...that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group. Potent agonists were identified, including some with a mGlu4 subtype preference, e.g., 17m (LSP1-2111) and 16g (LSP4-2022). Molecular modeling suggests that aromatic functional groups may bind at either one of the two chloride regulatory sites. These agonists may thus be considered as particular bitopic/dualsteric ligands. 17m was shown to reduce GABAergic synaptic transmission at striatopallidal synapses. We now demonstrate its inhibitory effect at glutamatergic parallel fiber–Purkinje cell synapses in the cerebellar cortex. Although these ligands have physicochemical properties that are markedly different from typical CNS drugs, they hold significant therapeutic potential.
Synchrotron microbeam radiation therapy (MRT), based on an inhomogeneous geometric and microscopic irradiation pattern of the tissues with high-dose and high-dose-rate x-rays, enhances the ...permeability of brain tumor vessels. This study attempted to determine the time and size range of the permeability window induced by MRT in the blood-brain (tumor) barrier.
Rats-bearing 9L gliomas were exposed to MRT, either unidirectional (tumor dose, 406 Gy) or bidirectional (crossfired) (2 × 203 Gy). We measured vessel permeability to molecules of 3 sizes (Gd-DOTA, Dotarem, 0.56 kDa; gadolinium-labeled albumin, ∼74 kDa; and gadolinium-labeled IgG, 160 kDa) by daily in vivo magnetic resonance imaging, from 1 day before to 10 days after irradiation.
An equivalent tumor dose of bidirectional MRT delivered from 2 orthogonal directions increased tumor vessel permeability for the smallest molecule tested more effectively than unidirectional MRT. Bidirectional MRT also affected the permeability of normal contralateral vessels to a different extent than unidirectional MRT. Conversely, bidirectional MRT did not modify the permeability of normal or tumor vessels for both larger molecules (74 and 160 kDa).
High-dose bidirectional (cross-fired) MRT induced a significant increase in tumor vessel permeability for small molecules between the first and the seventh day after irradiation, whereas permeability of vessels in normal brain tissue remained stable. Such a permeability window could facilitate an efficient and safe delivery of intravenous small molecules (≤0.56 kDa) to tumoral tissues. A permeability window was not achieved by molecules larger than gado-grafted albumin (74 kDa). Vascular permeability for molecules between these 2 sizes has not been determined.
RNA quality control (RQC) eliminates aberrant RNAs based on their atypical structure, whereas posttranscriptional gene silencing (PTGS) eliminates both aberrant and functional RNAs through the ...sequence-specific action of short interfering RNAs (siRNAs). The Arabidopsis thaliana mutant smd1b was identified in a genetic screen for PTGS deficiency, revealing the involvement of SmD1, a component of the Smith (Sm) complex, in PTGS. The smd1a and smd1b single mutants are viable, but the smd1a smd1b double mutant is embryo-lethal, indicating that SmD1 function is essential. SmD1b resides in nucleoli and nucleoplasmic speckles, colocalizing with the splicing-related factor SR34. Consistent with this, the smd1b mutant exhibits intron retention at certain endogenous mRNAs. SmD1 binds to RNAs transcribed from silenced transgenes but not nonsilenced ones, indicating a direct role in PTGS. Yet, mutations in the RQC factors UPFRAMESHIFT3, EXORIBONUCLEASE2 (XRN2), XRN3, and XRN4 restore PTGS in smd1b, indicating that SmD1 is not essential for but rather facilitates PTGS. Moreover, the smd1b mtr4 double mutant is embryo-lethal, suggesting that SmD1 is essential for mRNA TRANSPORT REGULATOR4-dependent RQC. These results indicate that SmD1 interplays with splicing, RQC, and PTGS. We propose that SmD1 facilitates PTGS by protecting transgene-derived aberrant RNAs from degradation by RQC in the nucleus, allowing sufficient amounts to enter cytoplasmic siRNA bodies to activate PTGS.
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