Multilingual Framework for Risk Assessment and Symptom Tracking (MRAST).

The importance and value of real-world data in healthcare cannot be overstated because it offers a valuable source of insights into patient experiences. Traditional patient-reported experience and outcomes measures (PREMs/PROMs) often fall short in addressing the complexities of these experiences due to subjectivity and their inability to precisely target the questions asked. In contrast, diary recordings offer a promising solution. They can provide a comprehensive picture of psychological well-being, encompassing both psychological and physiological symptoms. This study explores how using advanced digital technologies, i.e., automatic speech recognition and natural language processing, can efficiently capture patient insights in oncology settings. We introduce the MRAST framework, a simplified way to collect, structure, and understand patient data using questionnaires and diary recordings. The framework was validated in a prospective study with 81 colorectal and 85 breast cancer survivors, of whom 37 were male and 129 were female. Overall, the patients evaluated the solution as well made; they found it easy to use and integrate into their daily routine. The majority (75.3%) of the cancer survivors participating in the study were willing to engage in health monitoring activities using digital wearable devices daily for an extended period. Throughout the study, there was a noticeable increase in the number of participants who perceived the system as having excellent usability. Despite some negative feedback, 44.44% of patients still rated the app's usability as above satisfactory (i.e., 7.9 on 1-10 scale) and the experience with diary recording as above satisfactory (i.e., 7.0 on 1-10 scale). Overall, these findings also underscore the significance of user testing and continuous improvement in enhancing the usability and user acceptance of solutions like the MRAST framework. Overall, the automated extraction of information from diaries represents a pivotal step toward a more patient-centered approach, where healthcare decisions are based on real-world experiences and tailored to individual needs. The potential usefulness of such data is enormous, as it enables better measurement of everyday experiences and opens new avenues for patient-centered care.

Signal-to-noise ratio to assess magnitude, kinetics and impact on pharmacokinetics of the immune response to an adalimumab biosimilar.

Background: The antidrug antibody (ADA) signal-to-noise (S/N) ratio was explored as a novel immunogenicity measure to evaluate the immune response of healthy subjects to a single dose of GP2017, an adalimumab biosimilar. Methodology/results: Bioanalytical methods used for the analysis of ADA S/N ratios and ADA titers were validated for sensitivity, precision and drug interference. ADA S/N ratios strongly correlated with ADA titers. Correlations between ADA area under the curve and ADAmax and pharmacokinetics (PK) were stronger for ADA S/N ratio than for ADA titers. Conclusion: ADA S/N ratio allowed for a more sensitive evaluation of the magnitude and kinetics of the immune response, was better correlated with adalimumab PK and was superior to ADA titers in assessing the impact of the immune response on PK.

Establishing an Expert Consensus on Key Indicators of the Quality of Life among Breast Cancer Survivors: A Modified Delphi Study.

(1) Background: The needs of cancer survivors are often not reflected in practice. One of the main barriers of the use of patient-reported outcomes is associated with data collection and the interpretation of patient-reported outcomes (PROs) due to a multitude of instruments and measuring approaches. The aim of the study was to establish an expert consensus on the relevance and key indicators of quality of life in the clinical practice of breast cancer survivors. (2) Methods: Potential indicators of the quality of life of breast cancer survivors were extracted from the established quality of life models, depicting survivors' perspectives. The specific domains and subdomains of quality of life were evaluated in a two-stage online Delphi process, including an international and multidisciplinary panel of experts. (3) Results: The first round of the Delphi process was completed by 57 and the second by 37 participants. A consensus was reached for the Physical and Psychological domains, and on eleven subdomains of quality of life. The results were further supported by the additional ranking of importance of the subdomains in the second round. (4) Conclusions: The current findings can serve to optimize the use of instruments and address the challenges related to data collection and interpretation as the facilitators of the adaption in routine practice.

"I Don't Even Want to Come Out": the Suppressed Voices of Our Future and Opening the Lid on Sexual and Gender Minority Youth Workplace Discrimination in Europe: a Qualitative Study.

Introduction: In Europe, young sexual and gender minority (SGM) people continue to face discrimination in the labour sector despite advances in legislation towards their acceptance and equal treatment. Non-discrimination policy strategies helping SGM individuals are not equally enforced in all contexts, making it difficult for many SGM individuals to disclose their identity, hence undermining their health and well-being. Methods: Qualitative semi-structured interviews were conducted between October 2020 and February 2021 with 55 SGM youth (18-27 years) having work experience from Austria, Croatia, Serbia, Slovakia, Spain and the UK. Results: From the analysis, three overarching themes were significant: (1) societal discrimination played a major role in sociocultural factors and policy considerations, (2) workplace discrimination had distinct factors and impacts on SGM individuals and (3) SGM inclusion should use strategies to ensure workplace diversity and equality. Conclusions: SGM individuals from contexts of poor acceptance tended to hide their identity in the workplace, while transgender and non-binary individuals were prone to experience force-disclosure and discrimination in all aspects of employment. There is a lack of resolute reaction from policy makers in managing problems faced by SGM people in workplaces. New laws improving the status of SGM people need to be further adopted, staff training should be implemented, and managers are crucial in achieving an inclusive climate in the workplace.Policy ImplicationsIt is essential to implement policies on how to effectively handle problems faced by sexual and gender minority people in the workplace.

Patients-centered SurvivorShIp care plan after Cancer treatments based on Big Data and Artificial Intelligence technologies (PERSIST): a multicenter study protocol to evaluate efficacy of digital tools supporting cancer survivors.

BACKGROUND: It is encouraging to see a substantial increase in individuals surviving cancer. Even more so since most of them will have a positive effect on society by returning to work. However, many cancer survivors have unmet needs, especially when it comes to improving their quality of life (QoL). Only few survivors are able to meet all of the recommendations regarding well-being and there is a body of evidence that cancer survivors' needs often remain neglected from health policy and national cancer control plans. This increases the impact of inequalities in cancer care and adds a dangerous component to it. The inequalities affect the individual survivor, their career, along with their relatives and society as a whole. The current study will evaluate the impact of the use of big data analytics and artificial intelligence on the self-efficacy of participants following intervention supported by digital tools. The secondary endpoints include evaluation of the impact of patient trajectories (from retrospective data) and patient gathered health data on prediction and improved intervention against possible secondary disease or negative outcomes (e.g. late toxicities, fatal events). METHODS/DESIGN: The study is designed as a single-case experimental prospective study where each individual serves as its own control group with basal measurements obtained at the recruitment and subsequent measurements performed every 6 months during follow ups. The measurement will involve CASE-cancer, Patient Activation Measure and System Usability Scale. The study will involve 160 survivors (80 survivors of Breast Cancer and 80 survivors of Colorectal Cancer) from four countries, Belgium, Latvia, Slovenia, and Spain. The intervention will be implemented via a digital tool (mHealthApplication), collecting objective biomarkers (vital signs) and subjective biomarkers (PROs) with the support of a (embodied) conversational agent. Additionally, the Clinical Decision Support system (CDSS), including visualization of cohorts and trajectories will enable oncologists to personalize treatment for an efficient care plan and follow-up management. DISCUSSION: We expect that cancer survivors will significantly increase their self-efficacy following the personalized intervention supported by the m-HealthApplication compared to control measurements at recruitment. We expect to observe improvement in healthy habits, disease self-management and self-perceived QoL. Trial registration ISRCTN97617326. https://doi.org/10.1186/ISRCTN97617326 . Original Registration Date: 26/03/2021.

Step-wise approach to developing a scale-independent design space for functional tablet coating process.

The objective of this study is to present a practical example of a scale-independent design space development using a step-wise approach. A detailed description of the development process with a systematic outline of the main steps is provided. Design space is developed for film coating of tablets with moisture protective polyvinyl alcohol (PVA) based coating. The impact of scale-independent coating process parameters on the properties of film-coated tablets (FCT), i.e. water activity and film coating protection ability, and consequently on product long-term stability is explored. The main finding is that with model simplifications, a step-wise approach and rational development of scale-independent design space for the coating process, it is possible to efficiently predict, control, and optimize the long-term stability of a moisture sensitive product. However, the PVA moisture protective coating itself is recognized as having conflicting effects on product stability.

Elucidating molecular properties of kappa-carrageenan as critical material attributes contributing to drug dissolution from pellets with a multivariate approach.

Multivariate data analysis (MVDA) and artificial neural networks (ANN) are supporting statistical methodologies required for successful development and manufacturing of drug products. To address this purpose, a complex dataset from 49 industrially produced capsules filled with pellets was first analyzed through the development of a multiple linear regression model focused on determining raw material attributes or process parameters with a significant impact on drug dissolution. Based on the model, the following molecular and micrometrics properties of κ-carrageenan have been identified as critical material attributes with the highest contribution to drug dissolution: molecular weight and polydispersity index, viscosity, content of potassium ions, wettability, particle size, and density. The process parameters identified to control the drug dissolution behavior of pellets were amount of granulation liquid, torque of dry blend, spheronization parameters, and yields after screening. To further scrutinize the dataset, an ANN model was subsequently built, incorporating 29 batches addressing drug particle size and process parameters such as torque during granulation and spheronization time as critical factors. Finally, this study demonstrates the ability of MVDA and ANN to allow prediction of the key performance drivers influencing the drug dissolution of industrially developed capsules filled with pellets and it highlights their complementary relationship.

Diffuse large B-cell lymphoma: 10 years' real-world clinical experience with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone.

Treatment with rituximab plus a regimen of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) for patients with diffuse large B-cell lymphoma (DLBCL) has proven efficacy in clinical trials. The present study investigated its application in clinical practice. This single-center, retrospective database analysis included patients with DLBCL treated at the Slovenian Institute of Oncology Ljubljana between 2004 and 2013. Overall survival (OS) and progression-free survival (PFS) were assessed according to International Prognostic Index (IPI) and revised IPI (R-IPI) categories. Overall, 573 patients with DLBCL were included in the study (median follow-up, 45.3 months; range, 0.1-143.0). Patients were categorized as IPI 'low' (n=170; 30%), 'low-intermediate' (n=134; 23%), 'high-intermediate' (n=129; 23%) and 'high' (n=140; 24%) risk. R-IPI groups were indicated with 'very good' (n=59; 10%), 'good' (n=245; 43%) and 'poor' (n=269; 47%) prognosis. Ten-year OS and PFS rates were 51 and 72%, respectively; median OS was 124 months and median PFS was not reached. Ten-year OS rates were 80 and 87% in low-risk and 'very good' prognosis groups, respectively, and 30 and 37% in high-risk and poor prognosis patients, respectively. This analysis of patients with DLBCL indicated that many patients treated with R-CHOP and R-CHOP-like regimens in the real-world setting have excellent outcomes.

Scientific, statistical, practical, and regulatory considerations in design space development.

The quality by design (QbD) paradigm guides the pharmaceutical industry towards improved understanding of products and processes, and at the same time facilitates a high degree of manufacturing and regulatory flexibility throughout the establishment of the design space. This review article presents scientific, statistical and regulatory considerations in design space development. All key development milestones, starting with planning, selection of factors, experimental execution, data analysis, model development and assessment, verification, and validation, and ending with design space submission, are presented and discussed. The focus is especially on frequently ignored topics, like management of factors and CQAs that will not be included in experimental design, evaluation of risk of failure on design space edges, or modeling scale-up strategy. Moreover, development of a design space that is independent of manufacturing scale is proposed as the preferred approach.

Single Nucleotide Polymorphisms in Genes MACC1, RAD18, MMP7 and SDF-1a As Prognostic Factors in Resectable Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) represents one of the most common malignancies worldwide. Research has indicated that functional gene changes such as single nucleotide polymorphism (SNP) influence carcinogenesis and metastasis and might have an influence on disease relapse. The aim of our study was to evaluate the role of SNPs in selected genes as prognostic markers in resectable CRC. PATIENTS AND METHODS: In total, 163 consecutive patients treated surgically for CRC of stages I, II and III at the University Medical Centre in Maribor in 2007 and 2008 were investigated. DNA was isolated from formalin-fixed paraffin-embedded CRC tissue from the Department of Pathology and SNPs in genes SDF-1a, MMP7, RAD18 and MACC1 were genotyped using polymerase chain reaction followed by high resolution melting curve analysis or restriction fragment length polymorphism. RESULTS: We found worse disease-free survival (DFS) for patients with TT genotype of SNP rs1990172 in gene MACC1 (p = 0.029). Next, we found worse DFS for patients with GG genotype for SNP rs373572 in gene RAD18 (p = 0.020). Higher frequency of genotype GG of MMP7 SNP rs11568818 was found in patients with T3/T4 stage (p = 0.014), N1/N2 stage (p = 0.041) and with lymphovascular invasion (p = 0.018). For MACC1 rs1990172 SNP we found higher frequency of genotype TT in patients with T3/T4 staging (p = 0.024). Higher frequency of genotype GG of RAD18 rs373572 was also found in patients with T1/T2 stage with disease relapse (p = 0.041). CONCLUSIONS: Our results indicate the role of SNPs as prognostic factors in resectable CRC.