ABSTRACT
Background: A high incidence of venous thromboembolism (VTE) in COVID-19 has led to international recommendations for thromboprophylaxis. With limited data on Asian patients with COVID-19, the role of thromboprophylaxis remains unclear. Objectives: To investigate the in-hospital incidence of VTE in an Asian COVID-19 cohort, describe the VTE trend through successive COVID-19 waves (wild-type, delta, and omicron), and characterize the risk factors for VTE. Methods: We performed a retrospective observational cohort study of hospitalized COVID-19 adults from January 2020 to February 2022. Objectively confirmed VTE were reviewed to obtain VTE incidence and trend. Subset analysis of critical (intensive care), moderate (oxygen supplementation), and mild cases hospitalized ≥5 days was performed to investigate risk factors and in-hospital hazards of VTE. Results: Sixteen VTE events occurred among 3574 patients. Overall, VTE incidence was 0.45%, or 0.21% in mild, 3.60% in moderate, and 5.38% in critical infection. The maximum cumulative risk of VTE was 1.14% at 14 days for mild, 8.13% at 21 days for moderate, and 11.55% at 35 days for critical infection. Thromboprophylaxis use in mild, moderate, and critical cases was 5.7%, 28.8%, and 81.7%, respectively. In multivariable analysis, the severity of infection remained the strongest independent predictor of VTE. Compared with mild infection, the relative risk was 8.26 (95% CI, 2.26-30.16) for critical infection and 6.29 (95% CI, 1.54-25.67) for moderate infection. Conclusion: Overall, VTE incidence in Asian patients with COVID-19 is <1% across successive waves. Patients with moderate and critical infections are at greater risk for VTE and should be considered for routine thromboprophylaxis.
ABSTRACT
Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).
Subject(s)
Myeloproliferative Disorders , Polycythemia Vera , Thrombocythemia, Essential , Humans , Philadelphia Chromosome , Consensus , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/therapy , Polycythemia Vera/diagnosis , Polycythemia Vera/drug therapy , Polycythemia Vera/genetics , Thrombocythemia, Essential/drug therapy , Thrombocythemia, Essential/genetics , Interferon-alpha/genetics , Interferon-alpha/therapeutic useABSTRACT
PURPOSE OF REVIEW: The development of potent novel agents has improved outcomes for patients with multiple myeloma (MM). Heterogeneity of response to therapy, an expanding arsenal of treatment options, and cost are however major challenges for physicians making treatment decisions. Response-adapted therapy is hence an attractive strategy for sequencing of therapy in MM. Despite its successful application in other haematologic malignancies, response-adapted therapy is yet to become a standard of care for MM. We provide our perspective on response-adapted therapeutic strategies evaluated thus far and how they may be implemented and improved on in treatment algorithms of the future. RECENT FINDINGS: While older studies suggested that early response based on International Myeloma Working Group response criteria could impact long-term outcomes, recent data have contradicted these findings. The advent of minimal residual disease (MRD) as a powerful prognostic factor in MM has raised the promise of MRD-adapted treatment strategies. The development of more sensitive techniques for paraprotein quantification as well as imaging modalities to detect extramedullary disease is likely to change response assessment in MM. These techniques combined with MRD assessment may provide sensitive and holistic response assessments which could be evaluated in clinical trials. Response-adapted treatment algorithms have the potential to allow an individualised treatment strategy, maximising efficacy, while minimising toxicities and cost. Standardisation of MRD methodology, incorporation of imaging into response assessment, and the optimal management of MRD positive patients are key questions to be addressed in future trials.
Subject(s)
Hematologic Neoplasms , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Multiple Myeloma/drug therapy , Disease-Free Survival , Neoplasm, Residual/diagnosisABSTRACT
BACKGROUND: Grief and loss in the workplace setting often entail a culture of silence, which can be detrimental to the psychosocial and emotional functioning of the work unit. Oftentimes, in an effort to maintain the role of 'consummate professionals', expressions of negative emotions are suppressed to avoid awkwardness. However, employees are not automatons that can freely leave their emotions at the office lobby and then begin work. This piece details the experience of losing a long-time colleague and one team's efforts in aiding the organic development of a brief grief intervention for psychosocial care. METHOD: Named the Office 'Last Office', this process sought to (1) acknowledge the loss, (2) unpack emotions and (3) honour the memory of the deceased coworker and culminated with the (4) practical removal of their personal effects from their workstation for return to the family. CONCLUSION: This brief intervention borrows from the respectful sensitivity of the 'Last Office' or 'Laying Out' practice that nurses employ when working with the recently deceased and is a first step to informing and changing the current vocational climate regarding acknowledging grief within a workplace setting.
ABSTRACT
Whilst adaptive experts have well-researched beliefs and attitudes towards learning, what is unclear are the interactions that occur within the learning environment that constitute their learning experiences. The practice of geriatric medicine emphasises the interdisciplinary care of complex frail older adults. Our study sets out to understand the learning experiences of adaptive experts in geriatric medicine by examining how interactions at the intra-personal, inter-personal and organisational levels contributed to the development of adaptive expertise. We conducted an exploratory qualitative study through semi-structured interviews of 16 geriatricians experts from a tertiary hospital in Singapore. Data were analyzed via reflexive thematic analysis. The core essence of the learning experiences was described as a journey of 'knowing when we do not know', which was characterised by three themes: (i) Anchoring ethos of person-centric care where the experts drew upon their values to develop a holistic view of the patient beyond the medical domain, (ii) Enabling stance of being curious where their curiosity and openness to learning was nurtured through the practice of reflection, and with the benefit of time as a commodity and for development of expertise, and (iii) Scaffolding organisational culture of inquiry where an environment that is supportive of learning is built on the culture of psychological safety and the culture of mentoring. Taken together, our study highlighted the importance of interactions at the intra-personal, inter-personal and organisational levels in the learning experiences of adaptive experts.
Subject(s)
Learning , Mentoring , Humans , Aged , Attitude , Qualitative Research , MentorsABSTRACT
BACKGROUND: Haematological markers such as absolute lymphopenia have been associated with severe COVID-19 infection. However, in the literature to date, the cohorts described have typically included patients who were moderate to severely unwell with pneumonia and who required intensive care stay. It is uncertain if these markers apply to a population with less severe illness. We sought to describe the haematological profile of patients with mild disease with COVID-19 admitted to a single centre in Singapore. METHODS: We examined 554 consecutive PCR positive SARS-COV-2 patients admitted to a single tertiary healthcare institution from Feb 2020 to April 2020. In all patients a full blood count was obtained within 24â h of presentation. RESULTS: Patients with pneumonia had higher neutrophil percentages (66.5 ± 11.6 vs 55.2 ± 12.6%, p < 0.001), lower absolute lymphocyte count (1.5 ± 1.1 vs 1.9 ± 2.1 x109/L, p < 0.011) and absolute eosinophil count (0.2 ± 0.9 vs 0.7 ± 1.8 × 109/L, p = 0.002). Platelet counts (210 ± 56 vs 230 ± 61, p = 0.020) were slightly lower in the group with pneumonia. We did not demonstrate significant differences in the neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in patients with or without pneumonia. Sixty-eight patients (12.3%) had peripheral eosinophilia. This was more common in migrant workers living in dormitories. CONCLUSION: Neutrophilia and lymphopenia were found to be markers associated with severe COVID-19 illness. We did not find that combined haematological parameters: neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio, had any association with disease severity in our cohort of patients with mild-moderate disease. Migrant workers living in dormitories had eosinophilia which may reflect concurrent chronic parasitic infection.
Subject(s)
Blood Cell Count , COVID-19/blood , Pandemics , SARS-CoV-2 , Adult , Anthelmintics/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Dyslipidemias/epidemiology , Eosinophilia/epidemiology , Eosinophilia/etiology , Female , Fever/epidemiology , Fever/etiology , Housing , Humans , Hypertension/epidemiology , Hypoxia/epidemiology , Hypoxia/etiology , Male , Middle Aged , Neutrophils , Parasitic Diseases/drug therapy , Parasitic Diseases/epidemiology , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Singapore/epidemiology , Tertiary Care Centers/statistics & numerical data , Transients and Migrants/statistics & numerical data , Travel-Related Illness , Young Adult , COVID-19 Drug TreatmentABSTRACT
Spinning-induced rhabdomyolysis (SIR) is a well documented cause of exertional rhabdomyolysis. We aim to raise awareness and to call for preventive action towards avoidable healthcare costs associated with SIR. To this end, we describe three cases of SIR, associated healthcare costs and possible preventive strategies. We propose that community-based preventive measures should be considered in addressing the economic consequences of SIR.
Subject(s)
Physical Exertion , Rhabdomyolysis , Health Care Costs , Humans , Research , Rhabdomyolysis/chemically induced , Rhabdomyolysis/diagnosis , Rhabdomyolysis/therapySubject(s)
Autoantibodies/immunology , Dermatomyositis/diagnosis , Interferon-Induced Helicase, IFIH1/immunology , Skin Ulcer/etiology , Aged , Dermatomyositis/complications , Dermatomyositis/immunology , Dermatomyositis/pathology , Diagnosis, Differential , Female , Hand , Humans , Skin Ulcer/diagnosis , Skin Ulcer/pathologyABSTRACT
This Covid-19 pandemic has been a trying time for all countries, governments, societies, and individuals. The physical, social, and organizational infrastructure of healthcare systems across the world is being stressed. This pandemic has highlighted that the healthcare of the country is as strong as its weakest link and that no aspect of life, be it social or economic, is spared from this pandemic. The authors would like to highlight some of the lessons learned from Singapores management of the Covid-19 pandemic. During the Singaporean Covid-19 pandemic, public health policy planning was all encompassing in its coverage, involving various stakeholders in government and society. The important role of individuals, governments, industry, and primary healthcare practitioners when tackling COVID-19 are highlighted. Singapores management of the Covid-19 pandemic involved an approach that involved the whole of society, with a particular focus on supporting the vulnerable foreign worker population, which formed the majority of Covid-19 cases in the country. Hopefully amidst the trying times, valuable lessons are learnt that will be etched into medical history and collective memory. We hope to highlight these lessons for future generations, both for members of the public and fellow healthcare practitioners.
Subject(s)
COVID-19 , Public Health , Public Policy , Social Marginalization , COVID-19/epidemiology , COVID-19/prevention & control , Civil Defense/standards , Government Regulation , Health Services Needs and Demand/organization & administration , Humans , Public Health/methods , Public Health/standards , SARS-CoV-2 , Singapore/epidemiology , Transients and Migrants/statistics & numerical dataABSTRACT
BACKGROUND: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. METHOD AND RESULTS: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). CONCLUSIONS: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.
ABSTRACT
Modification of specificity of T cells for the use in adoptive transfer (CAR- or TCR-redirected T cells) has revolutionized the therapy of liquid tumors and some infectious diseases. However, several obstacles are still hampering the efficacy of such potent therapy, hence concurrent modification of the function is also required to obtain successful results. Here we show the use of splice-switching antisense oligonucleotides (SSOs) as a tool to transiently modify T cell function. We demonstrate the possibility to transfect SSOs and an exogenous TCR into primary human T cells in the same electroporation reaction, without affecting viability and function of the transfected T lymphocytes. Moreover, we show that SSOs targeting T cell-specific mRNAs induce the skipping of the targeted exons, and the reduction of the protein and consequent modification of T cell function. This technical work paves the way to the use of SSOs in immune cells, not only for the knockdown of the functional isoform of the targeted proteins, but also for the protein manipulation by elimination of specific domains encoded by targeted exons.
Subject(s)
Cell Survival/drug effects , Oligonucleotides, Antisense/pharmacology , T-Lymphocytes/immunology , Cell Survival/immunology , Exons/drug effects , Exons/genetics , Humans , Mutation/genetics , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/immunology , RNA Splicing/genetics , RNA Splicing/immunology , RNA, Messenger/genetics , T-Lymphocytes/drug effectsABSTRACT
BACKGROUND: The novel coronavirus disease (COVID-19) pandemic has led to rising death tolls and stressed healthcare systems, resulting in an unprecedented psychological stress on healthcare workers worldwide. However, the majority of studies only accounted for frontline healthcare workers with direct patient exposure. AIM: This study aims to look at the psychological impact of COVID-19 in a specific, vulnerable and yet hidden group of healthcare workers, namely laboratory healthcare workers who are at high risk exposure to SARS-CoV-2 virus from handling infected patients' blood samples, in addition to a marked increase in workload. METHOD: A multicentre study was conducted in Singapore via online questionnaire looking at psychological and physical impact of COVID-19 on laboratory healthcare workers. The Generalized Anxiety Disorder 7-item (GAD-7) scale, Zung Self-Rating Depression Scale (SDS) and Numeric rating scale on fear (NRS) were validated scores used in this study. Data analysis was performed using SPSS statistical software version 23 (IBM Corp). RESULTS: A total of 122 staffs participated and more than half of the cohort experienced mild to severe fear, anxiety and depression. Increase in depression score was also found to be associated with increased physical exhaustion (OR = 6.1, 95% CI 1.4-29.1, p = .02), loss of appetite (OR = 2.7, 95% CI 1.2-6.0, p = .02), poor sleep quality (OR = 7.5, 95% CI 2.9-19.4, p = .005), and the use of sedative (OR = 3.9, 95% CI 1.1-13.5, p = .03). CONCLUSIONS: Hence, it is imperative that prompt action needs to be taken to address the psychological needs of this vulnerable group of healthcare workers as the pandemic continues.
Subject(s)
Anxiety Disorders , COVID-19 , Depression , Fear , Medical Laboratory Personnel , Occupational Exposure/prevention & control , Anxiety Disorders/diagnosis , Anxiety Disorders/etiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/psychology , COVID-19/transmission , Cross-Sectional Studies , Depression/diagnosis , Depression/etiology , Diagnostic Self Evaluation , Female , Humans , Male , Medical Laboratory Personnel/psychology , Medical Laboratory Personnel/statistics & numerical data , Mental Health , Middle Aged , Occupational Health , SARS-CoV-2/isolation & purification , Singapore/epidemiology , Specimen Handling/psychology , Surveys and Questionnaires , WorkloadSubject(s)
Cellulitis/complications , Dengue/diagnosis , Hematoma/complications , Hemophilia A/etiology , Aged , Anti-Inflammatory Agents/therapeutic use , Blood Transfusion , Cellulitis/drug therapy , Cellulitis/pathology , Cyclophosphamide/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Prednisolone/therapeutic useABSTRACT
Adaptive expertise encompasses efficiency and innovation; however little is known about the state of research of adaptive expertise in medical education. Our scoping review summarizes existing evidence in the conceptual frameworks, development, and measurement for adaptive expertise. We searched Pubmed, MEDLINE, ERIC, CINAHL and PsycINFO for original research articles published from 1986 onwards in English. Given the heterogeneity of the studies, no quantitative syntheses were conducted and the articles were summarized qualitatively. Of the 48 articles that met inclusion criteria, 19 examined conceptual frameworks, 24 explored interventions supporting development and 5 examined measurement. Conceptual frameworks are consistent within and beyond health professions education. Factors influencing development include: predisposing factors such as knowledge (ability to integrate knowledge and innovate), beliefs and attitudes (high motivation and humility), enabling factors such as skills (people skills, implementing reflection and scholarly activities), resources such as curricular enablers (providing variability of cases, allowing flexibility to generate solutions, critical appraisal of textbooks) and reinforcing factors such as mentor-guided feedback and constant curricular review. Two validated measurement tools exist for adaptive expertise. Substantial research opportunities exist in studying interventions involving the development of adaptive expertise. Notable gaps exist in the development and validation of measurement tools.