ObjectiveThis study aims to assess and compare demographic and psychological factors and sleep status of frontline healthcare workers (HCWs) in relation to non-frontline HCWs.Design, settings, participants and outcomesThis cross-sectional study was conducted from 8 April 2020 to 17 April 2020 using an online survey across varied healthcare settings in Oman accruing 1139 HCWs.The primary and secondary outcomes were mental health status and sociodemographic data, respectively. Mental health status was assessed using the Depression, Anxiety, and Stress Scale (DASS-21), and insomnia was evaluated by the Insomnia Severity Index. Samples were categorised into the frontline and non-frontline groups. χ2 and t-tests were used to compare groups by demographic data. The Mantel-Haenszel OR was used to compare groups by mental health outcomes adjusted by all sociodemographic factors.ResultsThis study included 1139 HCWs working in Oman. While working during the pandemic period, a total of 368 (32.3%), 388 (34.1%), 271 (23.8%) and 211 (18.5%) respondents were reported to have depression, anxiety, stress and insomnia, respectively. HCWs in the frontline group were 1.5 times more likely to report anxiety (OR=1.557, p=0.004), stress (OR=1.506, p=0.016) and insomnia (OR=1.586, p=0.013) as compared with those in the non-frontline group. No significant differences in depression status were found between the frontline and non-frontline groups (p=0.201).ConclusionsTo our knowledge, this is the first study to explore the differential impacts of the COVID-19 pandemic on different grades of HCWs. This study suggests that frontline HCWs are disproportionally affected compared to non-frontline HCWs, with managing sleep–wake cycles and anxiety symptoms being highly endorsed among frontline HCWs. As psychosocial interventions are likely to be constrained owing to the pandemic, mental healthcare must first be directed to frontline HCWs.
We assessed the usefulness of 5-color multiparameter flow cytometry to detect leukemia-associated phenotypes (LAPs) in the bone marrow of patients with newly diagnosed acute myeloid leukemia (AML) and determined its usefulness for detection of minimal residual disease (MRD). Overall, 94% of patients (51/54) with AML had LAPs at diagnosis. The frequency of leukemic bone marrow/median frequency of LAPs in normal or regenerating bone marrow samples using maximum log difference statistics revealed that CD2, CD56, CD11b, CD7, and CD19 expression on AML blasts represented the most sensitive and reliable markers for detection of MRD. Serial dilutional experiments showed that the sensitivity level of immunophenotyping was between 10-4 and 10-5 and that the approach was highly reproducible. Immunophenotypic analysis using a CD45 gating strategy, 5-color staining, and an extensive panel of monoclonal antibodies allowed the identification of LAPs in 94% of AML cases, and these immunophenotypes can be used for MRD monitoring with a sensitivity limit of 10-4 to 10-5.
The presence of minimal residual disease (MRD) in the bone marrow (BM) of patients with acute myeloid leukemia (AML) following chemotherapy has been established by many studies to be strongly associated with relapse of leukemia. In addition, detection of MRD is the major objective of many of the newer diagnostic techniques used in malignant hematology. Because of the wide availability and conceptual straightforwardness of immunophenotyping, flow cytometry is the most accessible method for MRD detection. This review is not an overview of all MRD studies, but rather discusses the possibilities for optimizing MRD detection, the use of multiparameter flow cytometry (MFC) techniques in MRD detection, and the implications for future patient treatment. This review focuses on MRD detection in AML using MFC and discusses the reported correlations of MRD, clinical and biologic features of the disease, and outcome. In addition, it discusses the laboratory and clinical aspects of this approach.
IntroductionCurrently, needlestick injuries (NSIs) are one of the most important occupational hazards among healthcare workers (HCWs) globally. According to WHO, more than two million occupational exposures to sharp injuries occur among 35 million HCWs annually [1].NSIs increase the risk of over 20 types of infectious diseases among HCWs, including hepatitis B, hepatitis C, and HIV [2]. According to the Centers for Disease Control and Prevention (CDC) and European Agency for Safety and Health at Work (EU-OSHA) reports, there are more than 385,000 and 1,000,000 NSIs cases annually among hospital HCWs in the United States and Europe, respectively [3,4]. WHO statistics also show that NSIs cause 16,000, 66,000, and 1,000 cases of HCV, HBV, and HIV per year among HCWs, respectively [5]. The prevalence of various infectious diseases due to NSIs among HCWs is not a single and integrated phenomenon, rather is affected by several factors, such as vaccination rates among HCWs, access to appropriate worker protection
BackgroundAcute myeloid leukemia (AML) is a heterogeneous clonal disorder presenting with accumulation of proliferating undifferentiated blasts. Xenograft transplantation studies have demonstrated a rare population of leukemia-initiating cells called leukemic stem cells (LSCs) capable of propagating leukemia that are enriched in the CD34+/CD38− fraction. LSCs are quiescent, resistant to chemotherapy and likely responsible for relapse and therefore represent an ideal target for effective therapy. LSCs are reported to overexpress the alpha subunit of the IL-3 receptor (CD123) compared to normal CD34+/CD38− hematopoietic stem cells. It has not been demonstrated whether CD123-positive (CD34+/CD38−) subpopulation is enriched for any clonal markers of AML or any LSC properties. The aims of this study were to investigate whether FMS-like tyrosine kinase (FLT3)/internal tandem duplication (ITD) mutations are present at LSC level and whether FLT3/ITD mutation is confined to LSC as defined by CD34+/CD38−/CD123+ and not CD34+/CD38−/CD123−.MethodsThirty-four AML cases were analyzed by five-color flow cytometry and sequential gating strategy to characterize of CD34+/CD38−/CD123+ cells. These cells were sorted, analyzed by PCR, and sequenced for FLT3/ITD.ResultsIn this study, we confirm significant expression of CD123 in 32/34 cases in the total blast population (median expression = 86 %). CD123 was also expressed in the CD34+/CD38− cells (96 ± 2 % positive) from 28/32 for CD123+ AML. CD123 was not expressed/low in normal bone marrow CD34+/CD38− cells (median expression = 0 %, range (0–.004 %). AML samples were tested for FLT3/ITD (10 positive/25). FLT3/ITD+ AML cases were sorted into two putative LSC populations according to the expression of CD123 and analyzed for FLT3/ITD again in the stem cell fractions CD34+/CD38−/CD123+ and CD34+/CD38−/CD123−. Interestingly, FLT3/ITD was only detected in CD34+/CD38−/CD123+ (7/7) and not in CD34+/CD38−/CD123− subpopulation (6/7).ConclusionsThis finding shows that FLT3/ITD are present at LSC level and may be a primary and not secondary event in leukemogenesis, and the oncogenic events of FLT3/ITD happen at a cell stage possessing CD123. It shows that CD123 immunoprofiling provides further delineation of FLT3+ LSC clone. This novel finding provides a rationale for treatment involving CD123-targeting antibodies with intracellular FLT3 inhibitors directed against CD34+/CD38−/CD123+. This may result in more effective anti-LSC eradication.
Background: Multiparameter flow cytometry (MFC) has been shown to be a useful approach for detection of minimal residual disease (MRD). The aim of the study was to determine the optimal threshold that can separate patients into two groups in terms of leukemic residual cells and relapse status after induction and consolidation chemotherapy.Methods: Five-color MFC and receiver operating characteristics (ROC) analysis were used to determine the optimal threshold. This study analyzed 54 acute myeloid leukemia (AML) patients.Results: LAPs were detected in 51/54 (94%) patients. MRD was evaluated in the bone marrow (BM) in morphologic complete remission from 25 and 22 patients after induction and consolidation, respectively. The threshold discriminating MRD 2 from MRD 1 cases was set at 0.15% residual leukemic cells, a level that allowed optimal sensitivity and specificity for prediction of relapse, both at postinduction (P 5 0.05) and postconsolidation (P 5 0.009) time points using ROC analysis. MRD level postinduction not only influenced relapse-free survival (RFS) (P 5 0.004) but also overall survival (OS) (P 5 0.003). Multivariate analysis showed that MRD level postinduction was a powerful independent prognostic factor for both RFS (P 5 0.037) and OS (P 5 0.026).Conclusions: Using the ROC analysis, the threshold of 0.15% was defined as the optimal value in discriminating risk categories in AML, and postinduction MRD assessment is able to better predict disease outcome than consolidation. Therefore, MRD analysis by MFC could be used for refining the selection of therapeutic strategies and improving clinical outcome in individual patients. q
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