A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis

Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4% and 25.2%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3% for PFS and 46.5% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches

Case Specificity and Intervening Variables Affecting Diagnostic Accuracy within Two Similar Clinical Presentations

This study investigated the generalizability of diagnostic performance and problem solving strategy within and across cases from two similar clinical presentations (CP). Many variables have been described in medical education literature that influences the generalizability of diagnostic performance. This doctoral research further examined the effect of intervening variables in diagnostic performance. The variables studied were: disease difficulty, case typicality, CP, and problem solving strategy. Participants of the study were sixth year medical students enrolled in four universities in Saudi Arabia. Two types of data were analyzed, diagnostic performance scores obtained from written clinical vignettes and problem solving strategies abstracted from written think aloud exercises. Classical Test Theory (CTT) and Item Response Theory (IRT) were two measurement frameworks used to analyze the data and triangulate study findings. Variable reduction strategies were used to examine the construct of performance scores in comparison to the CP schemes. Cross-tabulation and Chi-square were used to investigate the consistency in using problem solving strategies within and across cases from two similar CPs. Also, Multi-Facet Rasch Modelling (MFRM) was employed to determine degree of impact on diagnostic performance by the independent variables. This study answered three research questions related to diagnostic generalizability and intervening variables that contribute to diagnostic performance. Most of the diseases included in this study showed high correlation coefficients and high discriminating measures. The estimated measures from two different measurement theories supported predictability of performance from one case to another. This research provides evidence that the diagnostic strategy utilized can alter diagnostic performance. Further support was found for schema-based instruction in medical schools to enhance student diagnostic performance. The research model illuminates some factors that influence diagnostic performance. Disease difficulty and type of CP were two variables found to alter diagnostic performance. Further research is required to identify other variables. Finally, these study findings set the base for future research. Directions for further investigation include: examining performance and problem solving strategy generalizability within and across dissimilar CPs; studying the effect of case typicality on diagnostic performance using MFRM; and including a broader sample that would include participants from medical schools that have different curricular models

Reliability and validity of an Arabic version of the revised two-factor study process questionnaire R-SPQ-2F

Objective: How students accomplish their learning and what they learn is an indicator of the quality of student learning. An insight into the learning approaches of a student could assist educators of the health profession in their planning for the first year of study. The aim of this study was to develop a reliable and valid Arabic version of the revised two-factor study process questionnaire. Materials and Methods: The translation of the revised two-Factor Study Process Questionnaire (R-SPQ-2F) into Arabic was done by an established forward-backward translation procedure. The Arabic version was then distributed to high school graduates applying for a place in the medical program at King Fahad Medical City. A total of 83 students voluntarily completed the questionnaire. The internal consistency and construct validity of the Arabic version of the R-SPQ-2F were computed. Results: The exploratory factor analysis revealed two components. The two factors were similar to the main scales described in the original English questionnaire. The main scales were the deep and surface approach. The items for the subscales (deep motive, deep strategy and surface motive, surface strategy) had a high internal consistency of more than 0.80. Conclusions: The results of this study should provide a valid and reliable instrument for the evaluation of the study approaches of Arabic speaking students

Development and validation of Simulation Scenario Quality Instrument (SSQI)

Abstract Background Due to the unmet need for valid instruments that evaluate critical components of simulation scenarios, this research aimed to develop and validate an instrument that measures the quality of healthcare simulation scenarios. Methods A sequential transformative mixed-method research design was used to conduct the study. The development and validation of the instrument involved two phases: the qualitative phase, which included defining the instrument's theoretical background and instrument construction, followed by the quantitative phase, where the instrument was piloted and validated. The qualitative study included 17 healthcare simulation experts, where three focus group was conducted, and the first version of the instrument was constructed based on the focus group analysis and the theoretical framework constructed using the literature review. During the quantitative phase, the instrument’s quantitative piloting included 125 healthcare simulation scenarios; then, the instrument went through construct validity and reliability testing. Results Content experts confirmed the theoretical model and instrument framework. The average item content validity index (I-CVI) scores and the average of the I-CVI scores (S-CVI/Ave) for all items on the scale or the average proportion relevance judged by all experts was 0.87. The conformity factor analysis results showed a good fit for the proposed 10-factor model (CFI (the comparative fit index) = 0.998, Tucker-Lewis index = 0.998, Root mean square error of approximation (RMSEA) = 0.061. The final instrument included ten domains: 1. Learning objectives, 2. Target group, 3. Culture, 4. Scenario case, 5. Scenario narrative briefing, 6. Scenario complexity, 7. Scenario flow, 8. Fidelity, 9. Debriefing, and 10. Assessment. The SSQI included 44 items that are rated on a 3-point scale (Meets Expectations = (2), Needs Improvement, (1), Inadequate (0)). Conclusion This validated and reliable instrument will be helpful to healthcare educators and simulation experts who want to develop simulation-based training scenarios and ensure the quality of written scenarios

A Progressive Model for Quality Benchmarks of Trainees’ Satisfaction in Medical Education: Towards Strategic Enhancement of Residency Training Programs at Saudi Commission for Health Specialties (SCFHS)

The latest developments in Sustainable Health focus on the provision of high quality medical training to health specialists, with a special focus on human factors. The need to promote effective Training Programs also reflects the job satisfaction needs of trainees. The objective of this study is to evaluate the trainees’ satisfaction with the quality of Training Programs and assess the degree of achievement based on the defined parameters to provide baseline data based on which strategies for improvement can be formulated. Our study was conducted in Saudi Arabia and our targeted population was residents in medical programs supervised by the Saudi Commission for the Health Specialties (SCFHS). The trainees’ response rate to the online survey was 27% (3696/13,688) and the key aspects of job satisfaction investigated include: Satisfaction with Academic Activities in the Center; Satisfaction with the Residents and Colleagues in the Center; Satisfaction with the Administrative Components in the Center; Satisfaction with the Training Programs; Satisfaction with the Specialty; Satisfaction with the Training Center; Satisfaction with the SCFHS. The main contribution of our work is a benchmark model for job satisfaction that can be used as a managerial tool for the enhancement of medical education with reference to the satisfaction of trainees. We analyze the key aspects and components of training satisfaction and we introduce our progressive model for Trainees’ Satisfaction in Medical Training. In future work, we intend to enhance the proposed framework with a set of key performance indicators as well as with a focused cause and effect focused survey on factors related to the key benchmark of this study

A Progressive Model for Quality Benchmarks of Trainees’ Satisfaction in Medical Education: Towards Strategic Enhancement of Residency Training Programs at Saudi Commission for Health Specialties (SCFHS)

The latest developments in Sustainable Health focus on the provision of high quality medical training to health specialists, with a special focus on human factors. The need to promote effective Training Programs also reflects the job satisfaction needs of trainees. The objective of this study is to evaluate the trainees’ satisfaction with the quality of Training Programs and assess the degree of achievement based on the defined parameters to provide baseline data based on which strategies for improvement can be formulated. Our study was conducted in Saudi Arabia and our targeted population was residents in medical programs supervised by the Saudi Commission for the Health Specialties (SCFHS). The trainees’ response rate to the online survey was 27% (3696/13,688) and the key aspects of job satisfaction investigated include: Satisfaction with Academic Activities in the Center; Satisfaction with the Residents and Colleagues in the Center; Satisfaction with the Administrative Components in the Center; Satisfaction with the Training Programs; Satisfaction with the Specialty; Satisfaction with the Training Center; Satisfaction with the SCFHS. The main contribution of our work is a benchmark model for job satisfaction that can be used as a managerial tool for the enhancement of medical education with reference to the satisfaction of trainees. We analyze the key aspects and components of training satisfaction and we introduce our progressive model for Trainees’ Satisfaction in Medical Training. In future work, we intend to enhance the proposed framework with a set of key performance indicators as well as with a focused cause and effect focused survey on factors related to the key benchmark of this study

A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis

Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4% and 25.2%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3% for PFS and 46.5% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches

Pancreatic tumors and immature immunosuppressive myeloid cells in blood and spleen: role of inhibitory co-stimulatory molecules PDL1 and CTLA4. An in vivo and in vitro study.

BACKGROUND: Blood and spleen expansion of immature myeloid cells (IMCs) might compromise the immune response to cancer. We studied in vivo circulating and splenic T lymphocyte and IMC subsets in patients with benign and malignant pancreatic diseases. We ascertained in vitro whether pancreatic adenocarcinoma (PDAC)-associated IMC subsets are induced by tumor-derived soluble factors and whether they are immunosuppressive focusing on the inhibitory co-stimulatory molecules PDL1 and CTLA4. METHODOLOGY AND PRINCIPAL FINDINGS: 103 pancreatic and/or splenic surgical patients were enrolled including 52 PDAC, 10 borderline and 10 neuroendocrine tumors (NETs). Lymphocytes and IMCs were analysed by flow cytometry in blood, in spleen and in three PDAC cell conditioned (CM) or non conditioned PBMC. PDL1 and CTLA4 were studied in 30 splenic samples, in control and conditioned PBMC. IMCs were FACS sorted and co-coltured with allogenic T lymphocytes. In PDAC a reduction was found in circulating CD8(+) lymphocytes (p = 0.004) and dendritic cells (p = 0.01), which were reduced in vitro by one PDAC CM (Capan1; p = 0.03). Blood myeloid derived suppressive cells (MDSCs) CD33(+)CD14(-)HLA-DR(-) were increased in PDAC (p = 0.022) and were induced in vitro by BxPC3 CM. Splenic dendritic cells had a higher PDL1 expression (p = 0.007), while CD33(+)CD14(+)HLA-DR(-) IMCs had a lower CTLA4 expression (p = 0.029) in PDAC patients. In vitro S100A8/A9 complex, one of the possible inflammatory mediators of immune suppression in PDAC, induced PDL1 (p = 0.018) and reduced CTLA4 expression (p = 0.028) among IMCs. IMCs not expressing CTLA4 were demonstrated to be immune suppressive. CONCLUSION: In PDAC circulating dendritic and cytotoxic T cells are reduced, while MDSCs are increased and this might favour tumoral growth and progression. The reduced CTLA4 expression found among splenic IMCs of PDAC patients was demonstrated to characterize an immune suppressive phenotype and to be consequent to the direct exposure of myeloid cells to pancreatic cancer derived products, S100A8/A9 complex in particular