1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma.

Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers can be identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and is already studied using RNA-seq. In this study, we generate a large (325,025 cells and 49 patients) single cell multi-omic dataset and jointly quantify ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identify an association between one plasma cell subtype with myeloma progression that we call relapsed/refractory plasma cells (RRPCs). These cells are associated with chromosome 1q alterations, TP53 mutations, and higher expression of PHF19. We also identify downstream regulation of cell cycle inhibitors in these cells, possible regulation by the transcription factor (TF) PBX1 on chromosome 1q, and determine that PHF19 may be acting primarily through this subset of cells.

Medical students' perspectives on and understanding of anesthesiology: a Canadian cross-sectional survey.

PURPOSE: In Canada, three out of 17 medical schools do not mandate an anesthesia rotation in their clerkship curriculum. Understanding the effects of a mandatory anesthesiology rotation is important in determining its value to the specialty and guiding decision-making for medical educators. We sought to determine whether a mandatory anesthesia rotation affected students' understanding of anesthesiology, as well as their perspectives on anesthesia. METHODS: We conducted an anonymous cross-sectional survey of Canadian medical students graduating in 2021. Our survey consisted of 46 questions related to student's perspectives of anesthesiology, understanding of anesthesia, their interest in the specialty, and participant's demographics. This included 16 Likert-scale questions, 19 quiz-style questions, four free-text response questions, and seven demographics questions. The survey was hosted by SurveyMonkey® (SurveyMonkey Inc., San Mateo, CA, USA) and distributed to the participants by each individual institution. RESULTS: We collected a total of 331 responses across 13 different Canadian medical schools, representing a 17.3% response rate of students surveyed and 11.7% of all graduating medical Canadian students in 2021. A mandatory rotation in anesthesiology was associated with a more positive perspective (P = 0.01) but not understanding (P = 0.07) of the specialty. A mandatory rotation was not related to students' application to anesthesiology at a statistically significant level (P = 0.06). CONCLUSIONS: The results of this national survey study show the benefits of including a mandatory clerkship rotation in anesthesiology, namely on increasing positive perceptions of the specialty, while also revealing avenues for future research and insights on how to further optimize a mandatory anesthesiology rotation in clerkship.

RéSUMé: OBJECTIF: Au Canada, trois facultés de médecine sur 17 n'exigent pas de stage clinique en anesthésie dans leur programme. Il est important de comprendre les effets d'un stage obligatoire en anesthésiologie afin de déterminer sa valeur pour la spécialité et d'orienter la prise de décision en matière d'éducation médicale. Nous avons cherché à déterminer si un stage obligatoire en anesthésie affectait la compréhension de l'anesthésiologie par les étudiant·es, ainsi que leurs points de vue sur l'anesthésie. MéTHODE: Nous avons mené un sondage transversal anonyme auprès d'étudiant·es en médecine qui ont obtenu leur diplôme en 2021 au Canada. Notre sondage comportait 46 questions portant sur leur point de vue sur l'anesthésiologie, leur compréhension de l'anesthésie, leur intérêt pour la spécialité et les caractéristiques démographiques des personnes interrogées. Le sondage comprenait 16 questions sur l'échelle de Likert, 19 questions courtes de type quiz, quatre questions à réponse libre et sept questions démographiques. Le sondage était hébergé par SurveyMonkey® (SurveyMonkey Inc., San Mateo, Californie, États-Unis) et a été distribué aux participant·es par chaque institution. RéSULTATS: Nous avons recueilli un total de 331 réponses dans 13 facultés de médecine canadiennes différentes, ce qui représente un taux de réponse de 17,3 % des étudiant·es interrogé·es et de 11,7 % de tous les étudiant·es en médecine diplômé·es en 2021 au Canada. Un stage obligatoire en anesthésiologie était associé à une perspective plus positive (P = 0,01) mais pas à une meilleure compréhension (P = 0,07) de la spécialité. Un stage obligatoire n'était pas lié aux demandes d'admission en anesthésiologie à un niveau statistiquement significatif (P = 0,06). CONCLUSION: Les résultats de cette enquête nationale montrent les avantages de l'inclusion d'un stage obligatoire en anesthésiologie, notamment pour accroître les perceptions positives de la spécialité, tout en révélant des pistes de recherche futures et des idées sur la façon d'optimiser davantage un stage clinique obligatoire en anesthésiologie.

Overall Survival in Patients With Multiple Myeloma in the U.S.: A Systematic Literature Review of Racial Disparities.

Multiple myeloma (MM) accounts for 10% of hematologic cancers in the U.S.; however, incidence and mortality occur disproportionately between racial groups in real-world settings. Our study's objective was to systematically characterize the disparities in overall survival (OS) among Black and White patients with MM in the US using real-world evidence studies. A systematic literature review was undertaken by searching Embase and MEDLINE for observational studies conducted in the US, published between January 1, 2015 and October 25, 2021, and reporting OS for Black and White patients with MM. Records were reviewed by 2 independent researchers. OS data were extracted as hazard ratios (HR), median survival, or %, with methods of adjustment, as reported. Evidence quality was assessed by data source, population, and variables for which HRs for risk of death were adjusted. We included 33 US studies comprising 410,086 patients (21.5% Black; 78.5% White) with MM. Receipt of treatment varied; however, most studies reported that patients either underwent stem cell transplant and/or received systemic therapy. HRs from 9 studies were considered "high quality" by comparing nationally representative, generalizable cohorts and adjusting for key prognostic, treatment, and/or socioeconomic factors. After adjustment, these data suggested that Black patients exhibit similar or superior survival outcomes compared with their White counterparts. When data are adjusted for important confounders, Black patients exhibit better or equal survival to White patients, indicating that similarities in patient populations and equal access to treatment can bridge the disparity in patient outcomes between races.

Identifying 1q amplification and PHF19 expressing high-risk cells associated with relapsed/refractory multiple myeloma.

Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers have been identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and has already been studied using RNA-seq. In this study a massive (325,025 cells and 49 patients) single cell multiomic dataset was generated with jointly quantified ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identified an association between one plasma cell subtype with myeloma progression that we have called relapsed/refractory plasma cells (RRPCs). These cells are associated with 1q alterations, TP53 mutations, and higher expression of PHF19. We also identified downstream regulation of cell cycle inhibitors in these cells, possible regulation of the transcription factor (TF) PBX1 on 1q, and determined that PHF19 may be acting primarily through this subset of cells.

Ethical considerations regarding the use of pooled data from electronic health records in general practice.

BACKGROUND: It is important that research conducted in general practice is ethical and technically robust. Electronic health records (EHRs) have high potential to contribute to research and policy that benefits both individual patients and the broader community. General practitioners are increasingly approached to make EHRs available for research, but they also have ethical and legal obligations to ensure personal information remains confidential and is handled safely. OBJECTIVE: The aim of this article is to discuss the ethical considerations associated with the pooling of general practice EHRs for research. DISCUSSION: There are associated benefits and potential risks to patients and practices when using pooled EHR data for research. Careful consideration and judgement are required to ensure ethical requirements are met, with particular attention to informed consent, data quality and confidentiality.

Treatment patterns and outcomes according to cytogenetic risk stratification in patients with multiple myeloma: a real-world analysis.

A clearer understanding of the prognostic implications of t(11;14) in multiple myeloma (MM) is needed to inform current and future therapeutic options. We utilized real-world data from a US database to examine treatment patterns and outcomes in patients by t(11;14) status compared with high- and standard-risk subgroups across different lines of therapy (LoT). This retrospective, observational cohort study used de-identified patient-level information from adults with MM and first-line treatment initiation between January 2011 and January 2020, followed until February 2020. The high-risk cohort comprised patients with high-risk genetic abnormalities per mSMART criteria (including those with co-occurring t(11;14)). Among 6138 eligible patients, 6137, 3160, and 1654 received first-, second-, and third-line treatments, respectively. Of 645 patients who had t(11;14), 69.1% had t(11;14) alone, while 30.9% had co-occurring high-risk abnormalities. Altogether, 1624 and 2544 patients were classified as high- and standard-risk, respectively. In the absence of biomarker-driven therapy, treatment patterns remain similar across LoT in high-risk, t(11;14)+, and standard-risk subgroups. Across all LoT, patient outcomes in the high-risk subgroup were less favorable than those in the t(11;14)+ and standard-risk subgroups. Thus, there is an opportunity for novel therapeutics targeted to t(11;14) and other defined subgroups to personalize MM therapy and optimize patient outcomes.

Organising medication discontinuation: a qualitative study exploring the views of general practitioners toward discontinuing statins.

BACKGROUND: Discontinuing medications is a complex decision making process and an important medical practice. It is a tool in reducing polypharmacy, reducing health system expenditure and improving patient quality of life. Few studies have looked at how general practitioners (GPs) discontinue a medication, in agreement with the patients, from a professional perspective. Three research questions were examined in this study: when does medication discontinuation occur in general practice, how is discontinuing medication handled in the GP's practice and how do GPs make decisions about discontinuing medication? METHODS: Twenty four GPs were interviewed using a maximum variation sample strategy. Participant observations were done in three general practices, for one day each, totalling approximately 30 consultations. RESULTS: The results show that different discontinuation cues (related to the type of consultation, medical records and the patient) create situations of dissonance that can lead to the GP considering the option of discontinuation. We also show that there is a lot of ambiguity in situations of discontinuing and that some GPs trialled discontinuing as means of generating more information that could be used to deal with the ambiguity. CONCLUSIONS: We conclude that the practice of discontinuation should be conceptualised as a continually evaluative process and one that requires sustained reflection through a culture of systematically scheduled check-ups, routinely eliciting the patient's experience of taking drugs and trialling discontinuation. Some policy recommendations are offered including supporting GPs with lists or handbooks that directly address discontinuation and by developing more person centred clinical guidelines that discuss discontinuation more explicitly.

General practitioners' decisions about discontinuation of medication: an explorative study.

Purpose - The purpose of this paper is to investigate how general practitioners' (GPs) decisions about discontinuation of medication are influenced by their institutional context. Design/methodology/approach - In total, 24 GPs were interviewed, three practices were observed and documents were collected. The Gioia methodology was used to analyse data, drawing on a theoretical framework that integrate the sensemaking perspective and institutional theory. Findings - Most GPs, who actively consider discontinuation, are reluctant to discontinue medication, because the safest course of action for GPs is to continue prescriptions, rather than discontinue them. The authors conclude that this is in part due to the ambiguity about the appropriateness of discontinuing medication, experienced by the GPs, and in part because the clinical guidelines do not encourage discontinuation of medication, as they offer GPs a weak frame for discontinuation. Three reasons for this are identified: the guidelines provide dominating triggers for prescribing, they provide weak priming for discontinuation as an option, and they underscore a cognitive constraint against discontinuation. Originality/value - The analysis offers new insights about decision making when discontinuing medication. It also offers one of the first examinations of how the institutional context embedding GPs influences their decisions about discontinuation. For policymakers interested in the discontinuation of medication, the findings suggest that de-stigmatising discontinuation on an institutional level may be beneficial, allowing GPs to better justify discontinuation in light of the ambiguity they experience.

Pandemic (H1N1) 2009 infection in patients with hematologic malignancy.

To assess outcomes of patients with hematologic malignancy and pandemic (H1N1) 2009 infection, we reviewed cases during June-December 2009 at the University of California San Francisco Medical Center. Seventeen (63%) and 10 (37%) patients had upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI), respectively. Cough (85%) and fever (70%) were the most common signs; 19% of patients had nausea, vomiting, or diarrhea. Sixty-five percent of URTI patients were outpatients; 35% recovered without antiviral therapy. All LRTI patients were hospitalized; half required intensive care unit admission. Complications included acute respiratory distress syndrome, pneumomediastinum, myocarditis, and development of oseltamivir-resistant virus; 3 patients died. Of the 3 patients with nosocomial pandemic (H1N1) 2009, 2 died. Pandemic (H1N1) 2009 may cause serious illness in patients with hematologic malignancy, primarily those with LRTI. Rigorous infection control, improved techniques for diagnosing respiratory disease, and early antiviral therapy can prevent nosocomial transmission and optimize patient care.