A single centre experience of using venetoclax and azacitidine in the treatment of AML

Background: The combination of venetoclax and azacitidine was licensed as a treatment regime for AML during the COVID-19 pandemic and has only been available for a short period of time. It has been widely adopted, including by our centre, for use in older adults and those with multiple co-morbidities, for whom intensive treatment might not be appropriate, but where low-intensity treatment or palliative care is also considered inappropriate. We feel that our patient cohort has been experiencing a lot of cytopaenias with the regime and thus treatment has been de-escalated more commonly than seen in the VIALE-A trial1 and so decided to carry out an audit of our practice. Method(s): Patients were identified by our pharmacy colleagues as having had Blueteq forms completed for venetoclax-azacitidine treatment. We then looked at their electronic medical records to ascertain their age, co-morbidities, treatment received, any treatment modifications made (and reasons for these adjustments), disease course and time until death. Result(s): We identified 22 patients who have received treatment with venetoclax and azacitidine, since October 2020. Eleven of these patients are now deceased (50%), with causes of death attributable to progressive disease or infection. The median age of our patient population was 72 years old (range of 51-84). The maximal number of cycles of venetoclax-azacitidine that have been delivered to a single patient is 12 (with cessation following disease progression). 9/22 patients had no dose modifications made to treatment, but of these, six patients only received one cycle of treatment (prior to progressive disease or death from sepsis). The rest of the patients (13) have had dose reductions to shorter courses of venetoclax (to between 21 days and 7 days) or have been changed to azacitidine alone (5/13 patients). One of our 22 patients has now received an allograft. Conclusion(s): Our patients routinely receive posaconazole prophylaxis, and thus a dose of 100 mg venetoclax (due to the known interaction), rather than the 400 mg dose used in the VIALE-A trial1-it may be that this, (and that it is equivalent to an actual dose of greater than 400 mg), is the reason behind the increased incidence of cytopaenias and increased need to de-escalate treatment. In the future it would be helpful and informative to compare our practice to that of other centres.

Are researchers in academic medicine flourishing? A survey of midcareer Ph.D. and physician investigators.

Introduction: Midcareer research faculty are a vital part of the advancement of science in U.S. medical schools, but there are troubling trends in recruitment, retention, and burnout rates. Methods: The primary sampling frame for this online survey was recipients of a single R01 or equivalent and/or K-award from 2013 to 2019. Inclusion criteria were 3-14 years at a U.S. medical school and rank of associate professor or two or more years as assistant professor. Forty physician investigators and Ph.D. scientists volunteered for a faculty development program, and 106 were propensity-matched controls. Survey items covered self-efficacy in career, research, work-life; vitality/burnout; relationships, inclusion, trust; diversity; and intention to leave academic medicine. Results: The majority (52%) reported receiving poor mentoring; 40% experienced high burnout and 41% low vitality, which, in turn, predicted leaving intention (P < 0.0005). Women were more likely to report high burnout (P = 0.01) and low self-efficacy managing work and personal life (P = 0.01) and to be seriously considering leaving academic medicine than men (P = 0.003). Mentoring quality (P < 0.0005) and poor relationships, inclusion, and trust (P < 0.0005) predicted leaving intention. Non-underrepresented men were very likely to report low identity self-awareness (65%) and valuing differences (24%) versus underrepresented men (25% and 0%; P < 0.0005). Ph.D.s had lower career advancement self-efficacy than M.D.s (P < .0005). Conclusions: Midcareer Ph.D. and physician investigators faced significant career challenges. Experiences diverged by underrepresentation, gender, and degree. Poor quality mentoring was an issue for most. Effective mentoring could address the concerns of this vital component of the biomedical workforce.

The utilization of palm kernel shells and waste plastics in asphaltic mix for sustainable pavement construction. (Special Issue: Technology and innovation for a post COVID recovery and growth: the contribution of industry and academia.)

Natural aggregates are being depleted due to the high demand for road and building construction and need to be replaced with alternative materials. This study investigated the potential of using Palm kernel shells (PaKS) as a partial replacement for natural aggregates (NA) and waste plastics (WP) as a binder. The physical and volumetric properties of the different asphaltic mixes (AM) were assessed using the Marshall Method. The bitumen content of the mix design samples was varied from 4.0% to 7.5% of the total weight of aggregates utilized. According to the Marshall parameters, at 5.5% bitumen content, the maximum Marshall Stability value of the different mix designs increased from 9.8 kN to 12.1 kN and the flow value increased from 3.0 mm to 3.7 mm. The experimental results based on the optimum bitumen content determined by the Marshall method demonstrate that PaKS and WP can be utilized to modify AM. However, additional tests will be needed to evaluate the use of this composition in road construction.

Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

A multidisciplinary approach to improvement of a bone marrow biopsy service: advice from both service users and service providers

Local patient complications of bone marrow biopsy (BMB) prompted a review of our service in a UK tertiary haematology centre that performs approximately 1000 BMBs per year. BMB is a necessary diagnostic tool within haematology;it is invasive, with low rates of serious adverse events. However, there is uncertainty around less severe but patient-relevant complications. An online survey of staff who request or perform BMB was undertaken in advance of discussion of the complication events at a morbidity and mortality meeting. The survey was fed back at a subsequent departmental education meeting. Survey comments and feedback during the meetings were recorded. This provided a forum for extensive discussion;staff expressed a desire for change in the service and offered many ideas to improve service efficiency, patient experience and to mitigate risk. A multidisciplinary team (MDT) was motivated to form a service improvement group. A patient survey was distributed to 100 patients that had recently used the service;44 surveys were returned. Feedback was mostly positive and results were shared with staff. Information about the procedure, feeling reassured or relaxed and minimising pain was mentioned by several patients, reminding us that addressing patient uncertainty, anxiety and analgesia is imperative. Additional activities were undertaken to understand how the service currently runs. Day unit nursing and medical, administration and laboratory staff met to map the process from BMB request to results. A time in motion study of several BMBs was performed to record the time taken for each procedure and how this time was divided. From preparation to documentation, the range was 68-90 min. The standard time allocated to a doctor who is often unassisted in the procedure room is 45 min. A snapshot audit identified that some of the time taken was to make the laboratory requests or review anticoagulation, which are intended to be done in advance;occasionally, cancellations resulted. We have reviewed this data to identify targets to increase efficiency and staffing support. To date, a new patient information leaflet has been created to address the clarity and depth of information provided to patients, including more detailed postprocedural advice and departmental contact details. A preprocedure checklist will be trialled as suggested by a survey respondent. The Standard Operating Procedure is under review to clarify roles, responsibilities and processes, particularly in the context of increasing molecular monitoring out of region. Incident reporting of complications has been encouraged. A 'Patient Safety Registrar' will work with our Patient Safety Manager to oversee quarterly discussions of incidents within our departmental teaching because we have found that this improved staff engagement during this project. We have found that this MDT approach integrated into departmental teaching has resulted in excellent engagement, idea generation and momentum despite the staffing pressures during the Covid-19 pandemic. Progress will be reviewed after a year.

Facilitating safe discharge through predicting disease progression in moderate COVID-19: a prospective cohort study to develop and validate a clinical prediction model in resource-limited settings (preprint)

BackgroundIn locations where few people have received COVID-19 vaccines, health systems remain vulnerable to surges in SARS-CoV-2 infections. Tools to identify patients suitable for community-based management are urgently needed. MethodsWe prospectively recruited adults presenting to two hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex and SpO2) and one of seven shortlisted biochemical biomarkers measurable using near-patient tests (CRP, D-dimer, IL-6, NLR, PCT, sTREM-1 or suPAR), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration and clinical utility of the models in a temporal external validation cohort. Findings426 participants were recruited, of whom 89 (21{middle dot}0%) met the primary outcome. 257 participants comprised the development cohort and 166 comprised the validation cohort. The three models containing NLR, suPAR or IL-6 demonstrated promising discrimination (c-statistics: 0{middle dot}72 to 0{middle dot}74) and calibration (calibration slopes: 1{middle dot}01 to 1{middle dot}05) in the validation cohort, and provided greater utility than a model containing the clinical parameters alone. InterpretationWe present three clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources. FundingMedecins Sans Frontieres, India. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSA living systematic review by Wynants et al. identified 137 COVID-19 prediction models, 47 of which were derived to predict whether patients with COVID-19 will have an adverse outcome. Most lacked external validation, relied on retrospective data, did not focus on patients with moderate disease, were at high risk of bias, and were not practical for use in resource-limited settings. To identify promising biochemical biomarkers which may have been evaluated independently of a prediction model and therefore not captured by this review, we searched PubMed on 1 June 2020 using synonyms of "SARS-CoV-2" AND ["biomarker" OR "prognosis"]. We identified 1,214 studies evaluating biochemical biomarkers of potential value in the prognostication of COVID-19 illness. In consultation with FIND (Geneva, Switzerland) we shortlisted seven candidates for evaluation in this study, all of which are measurable using near-patient tests which are either currently available or in late-stage development. Added value of this studyWe followed the TRIPOD guidelines to develop and validate three promising clinical prediction models to help clinicians identify which patients presenting with moderate COVID-19 can be safely managed in the community. Each model contains three easily ascertained clinical parameters (age, sex, and SpO2) and one biochemical biomarker (NLR, suPAR or IL-6), and would be practical for implementation in high-patient-throughput low resource settings. The models showed promising discrimination and calibration in the validation cohort. The inclusion of a biomarker test improved prognostication compared to a model containing the clinical parameters alone, and extended the range of contexts in which such a tool might provide utility to include situations when bed pressures are less critical, for example at earlier points in a COVID-19 surge. Implications of all the available evidencePrognostic models should be developed for clearly-defined clinical use-cases. We report the development and temporal validation of three clinical prediction models to rule-out progression to supplemental oxygen requirement amongst patients presenting with moderate COVID-19. The models are readily implementable and should prove useful in triage and resource allocation. We provide our full models to enable independent validation.

Interventions to improve headcount during covid-19 lockdown in South Africa

Background: The world was overcome by the COVID-19 pandemic from late 2019. South Africa entered into a country wide lockdown level 5 from March 26 to April 16, 2020. Public health facilities were greatly affected as they experienced reduced facility headcounts, which resulted in reduced HIV testing services (HTS), reduced patients attending their follow-up visits, and this also impacted the viral load completions. Methods: This was a retrospective review that analyzed the trends and the impact COVID-19 had on the headcount of primary health care (PHC) facilities and the number of patients accessing HTS and the Total Remaining on ART (TROA). In order to view the facility headcount and HTS trends on the same scale, for graphical representation the monthly figures have been indexed to their values in July 2019 (Jul 2019 = 100), prior to the impact of COVID-19 and the typical seasonal decline in activity during the holiday period. Results: Facility headcount dropped during the COVID-19 period (Mar 20, 0.98 to Apr 20, 0.73);and it is clear that the HTS trends (Mar 20, 0.89 to Apr 20, 0.47) mirror the headcount trends (Figure 1). However, the total remaining on ART remained relatively stable during this period;demonstrating successful programme efforts towards retention. These activities included case management of clients, community ART delivery, SMS reminders, extension of CCMDD (Centralised Chronic Medication Dispensing and Distribution) scripts, multi-month scripting and dispensing, improved appointment systems in facilities where we had filing interns, data quality improvement activities during this period and daily tracking with the district teams. Historically we have seen that HTS habitually drops during the holiday periods of December and April but starts picking up and follows the headcount trends. This year Level-5 lockdown brought on a steep drop with a strong recovery once lockdown restrictions eased, albeit not totally to former levels. Conclusion: Therefore, despite drastic drops in headcount from April 2020 to September 2020 as compared to 2019, the stability of TROA shows that implemented retention strategies have had a positive impact on the retention of patients during a pandemic.

The Virtual Hospitalist: a Critical Innovation During the COVID-19 Crisis.

A virtual hospitalist program expanded our ability to confront the challenges of the COVID-19 crisis at the epicenter of the pandemic in New York City. In concert with on-site hospitalists and redeployed physicians, virtual hospitalists aimed to expand capacity while maintaining high-quality care and communication. The program addressed multiple challenges created by our first COVID-19 surge: high patient census and acuity; limitations of and due to personal protective equipment; increased communication needs due to visitor restrictions and the uncertain nature of the novel disease, and limitations to in-person work for some physicians. The program created a mechanism to train and support new hospitalists and provide and expand palliative care services. We describe how our virtual hospitalist program operated during our COVID-19 surge in April and May 2020 and reflect on potential roles of virtual hospitalists after the COVID-19 crisis passes.

Shared Mental Models: Insights and Perspectives on Ideologies and Institutions: International review for social sciences;internationale Zeitschrift für Sozialwissenschaften

SUMMARYThis article leads off a special symposium comprised of a select group of public choice economists and political scientists that assembled to reflect on the important contribution that Arthur T. Denzau and Douglass C. North’s seminal piece on Shared Mental Models (1993) has made over the last quarter of a century. Relatedly, we apply concepts from Denzau and North’s Shared Mental Models to suggest a modified model of the Nash equilibrium used in non‐cooperative game theory to help us operationalize the “learning path” by which we can move from “siloed” thinking to a wider “systems” view of organizations, our environment, and indeed, the world. Our model has implications for the way we respond to economic crises, financial meltdowns, and global health epidemics, such as the COVID‐19 pandemic.