Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation.

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRDpos) post-induction. MRDpos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRDneg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRDpos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRDpos intermediate-risk AML patients.

Evolution from an antecedent chronic myeloid malignancy does not impact survival outcomes in NPM1-mutated AML.

Nucleophosmin-1 (NPM1)-mutated AML is a molecularly defined subtype typically associated with favorable treatment response and prognosis; however, its prognostic significance in AML evolving from an antecedent chronic myeloid malignancy is unknown. This study's primary objective was to determine the impact of mutated NPM1 on the prognosis of AML evolving from an antecedent chronic myeloid malignancy. We conducted a retrospective chart review including patients with NPM1-mutated de novo and sAML. sAML was defined as those with a preceding chronic-phase myeloid malignancy before diagnosis of AML. Of 575 NPM1-mutated patients eligible for inclusion in our study, 51 (8.9%) patients were considered to have sAML. The median time from diagnosis of NPM1-mutated chronic myeloid malignancy to sAML evolution was 3.6 months (0.5-79.3 months). No significant differences in leukemia-free (2-year LKFS 52.0% vs. 51.2%, p = .9922) or overall survival (2-year OS 56.3% vs. 49.4%, p = .4246) were observed between patients with NPM1-mutated de novo versus sAML. Our study suggests that evolution from a preceding myeloid malignancy is not a significant predictor of poor prognosis in the setting of an NPM1 mutation. Our study demonstrated a short time to progression to sAML in most patients, which further supports the consideration of NPM1 as an AML-defining mutation.

Body composition assessment by artificial intelligence can be a predictive tool for short-term postoperative complications in Hartmann's reversals.

BACKGROUND: Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann's reversal procedure in the prediction of short-term postoperative complications. METHODS: A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2 < 38.5 cm2/m2 in women and < 52.4 cm2/m2 in men. RESULTS: Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%) underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present. CONCLUSION: Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann's reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients.

Patient and Provider Satisfaction with Asynchronous Versus Synchronous Telepsychiatry in Primary Care: A Secondary Mixed-Methods Analysis of a Randomized Controlled Trial.

Background: Asynchronous telepsychiatry (ATP) consultations are a novel form of psychiatric consultation. Studies comparing patient and provider satisfaction for ATP with that for synchronous telepsychiatry (STP) do not exist. Methods: This mixed-methods study is a secondary analysis of patients' and primary care providers' (PCPs) satisfaction from a randomized clinical trial of ATP compared with STP. Patients and their PCPs completed satisfaction surveys, and provided unstructured feedback about their experiences with either ATP or STP. Differences in patient satisfaction were assessed using mixed-effects logistic regression models, and the qualitative data were analyzed using thematic analysis with an inductive coding framework. Results: Patient satisfaction overall was high with 84% and 97% of respondents at 6 months reported being somewhat or completely satisfied with ATP and STP, respectively. Patients in the STP group were more likely to report being completely satisfied, to recommend the program to a friend, and to report being comfortable with their care compared with ATP (all p < 0.05). However, there was no difference between the patients in ATP and STP in perceived change in clinical outcomes (p = 0.51). The PCP quantitative data were small, and thus only summarized descriptively. Conclusions: Patients expressed their overall satisfaction with both STP and ATP. Patients in ATP reported more concerns about the process, likely because feedback after ATP was slower than that after STP consultations. PCPs had no apparent preference for STP or ATP, and reported implementing the psychiatrists' recommendations for both groups when such recommendations were made, which supports our previous findings. Trial Registration: ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.

Venous thromboembolism incidence associated with pegylated asparaginase (ASP) compared to the native L-ASP: A retrospective analysis with an ASP-based protocol in adult patients with acute lymphoblastic leukaemia.

Venous thromboembolism (VTE) is a well-known complication in patients with acute lymphoblastic leukaemia (ALL) receiving asparaginase (ASP)-based chemotherapy, including the ASP-intensive Dana-Farber Cancer Institute (DFCI) 91-01 protocol for adults. Since 2019, native L-ASP is no longer available in Canada and was replaced by pegylated (PEG)-ASP. To determine whether the incidence of VTE has changed since switching from L-ASP to PEG-ASP, we conducted a single-centred retrospective cohort study. We included 245 adult patients with Philadelphia chromosome negative ALL between 2011 and 2021, with 175 from the L-ASP group (2011-2019) and 70 from the PEG-ASP group (2018-2021). During Induction, 10.29% (18/175) of patients who received L-ASP developed VTE, whereas 28.57% (20/70) of patients who received PEG-ASP developed VTE (p = 0.0035; odds ratio [OR] 3.35, 95% confidence interval [CI] 1.51-7.39), after adjusting for line type, gender, history of VTE, platelets at diagnosis. Similarly, during Intensification, 13.64% (18/132) of patients had VTE on L-ASP while 34.37% (11/32) of patients on PEG-ASP developed VTE (p = 0.0096; OR 3.96, 95% CI 1.57-9.96 with multivariable analysis). We found that PEG-ASP is associated with a higher incidence of VTE compared to L-ASP, both during Induction and Intensification, despite the administration of prophylactic anticoagulation. Further VTE mitigation strategies are needed in particular for adult patients with ALL receiving PEG-ASP.

An integrative systems biology approach to overcome venetoclax resistance in acute myeloid leukemia.

The over-expression of the Bcl-2 protein is a common feature of many solid cancers and hematological malignancies, and it is typically associated with poor prognosis and resistance to chemotherapy. Bcl-2-specific inhibitors, such as venetoclax, have recently been approved for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma, and they are showing promise in clinical trials as a targeted therapy for patients with relapsed or refractory acute myeloid leukemia (AML). However, successful treatment of AML with Bcl-2-specific inhibitors is often followed by the rapid development of drug resistance. An emerging paradigm for overcoming drug resistance in cancer treatment is through the targeting of mitochondrial energetics and metabolism. In AML in particular, it was recently observed that inhibition of mitochondrial translation via administration of the antibiotic tedizolid significantly affects mitochondrial bioenergetics, activating the integrated stress response (ISR) and subsequently sensitizing drug-resistant AML cells to venetoclax. Here we develop an integrative systems biology approach to acquire a deeper understanding of the molecular mechanisms behind this process, and in particular, of the specific role of the ISR in the commitment of cells to apoptosis. Our multi-scale mathematical model couples the ISR to the intrinsic apoptosis pathway in venetoclax-resistant AML cells, includes the metabolic effects of treatment, and integrates RNA, protein level, and cellular viability data. Using the mathematical model, we identify the dominant mechanisms by which ISR activation helps to overcome venetoclax resistance, and we study the temporal sequencing of combination treatment to determine the most efficient and robust combination treatment protocol.

Mutational profile, outcomes, and impact of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia and inconclusive cytogenetic analysis.

BACKGROUND: Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported. METHODS: We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019. Patients with any documented cytogenetic abnormalities were excluded. Targeted next generation sequencing (NGS) was performed in all patients. Baseline characteristics, mutation profile, and outcomes were compared between patients with normal cytogenetics(NC) and those with IC. RESULTS: Sixty-one patients (males 39.3%; median age 59 years) had IC at diagnosis. The proportion of patients with mutations in genes with proven prognostic impact were not different between AML patients with IC and NC. AML patients with NC were more likely to harbor the prognostically favorable NPM1mut /FLT3-ITDwt mutational combination conferring "favorable" risk status. As a result, a larger proportion of patients in the IC group underwent allogeneic hematopoietic stem cell transplantation (allo HCT; 54.1% vs. 39.6%; p = .02). The 2-year RFS (55.9% vs. 58.5%; p = .29) and OS (61.9% vs. 66.9%; p = .48) were similar in IC and NC patients. There was no difference in survival of patients who underwent allo HCT when compared with patients who did not (p = .99). CONCLUSIONS: Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.

Impact of Geographical Distance from Quaternary Treatment Center on Clinical Trial Participation, Intensive Induction Chemotherapy, and Outcomes in Patients with Newly Diagnosed Acute Myeloid Leukemia.

INTRODUCTION: Care for patients with acute myeloid leukemia (AML) is centralized in the Ontario single-payer public healthcare system, with intensive induction chemotherapy and clinical trials only offered at specialized cancer centers with large catchment areas. METHODS: We therefore conducted a retrospective single-center review of all AML patients assessed at a large specialized cancer center in Ontario, Canada. RESULTS: Between 2012 and 2017, 1,310 patients were assessed by our center for upfront AML therapy. The median distance was 33.1 km, with 29% of patients living more than 50 km away from the center. There was no significant difference in probability of intensive induction chemotherapy or clinical trial by distance from center, both in univariate and multivariable analysis adjusting for age, sex, cytogenetics and molecular testing, and performance status. There was no significant difference in overall survival by distance from center on univariate and multivariable analysis. CONCLUSION: In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, participation in clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single-payer environment.

Findings and Guidelines on Provider Technology, Fatigue, and Well-being: Scoping Review.

BACKGROUND: Video and other technologies are reshaping the delivery of health care, yet barriers related to workflow and possible provider fatigue suggest that a thorough evaluation is needed for quality and process improvement. OBJECTIVE: This scoping review explored the relationship among technology, fatigue, and health care to improve the conditions for providers. METHODS: A 6-stage scoping review of literature (from 10 databases) published from 2000 to 2020 that focused on technology, health care, and fatigue was conducted. Technologies included synchronous video, telephone, informatics systems, asynchronous wearable sensors, and mobile health devices for health care in 4 concept areas related to provider experience: behavioral, cognitive, emotional, and physical impact; workplace at the individual, clinic, hospital, and system or organizational levels; well-being, burnout, and stress; and perceptions regarding technology. Qualitative content, discourse, and framework analyses were used to thematically analyze data for developing a spectrum of health to risk of fatigue to manifestations of burnout. RESULTS: Of the 4221 potential literature references, 202 (4.79%) were duplicates, and our review of the titles and abstracts of 4019 (95.21%) found that 3837 (90.9%) were irrelevant. A full-text review of 182 studies revealed that 12 (6.6%) studies met all the criteria related to technology, health care, and fatigue, and these studied the behavioral, emotional, cognitive, and physical impact of workflow at the individual, hospital, and system or organizational levels. Video and electronic health record use has been associated with physical eye fatigue; neck pain; stress; tiredness; and behavioral impacts related to additional effort owing to barriers, trouble with engagement, emotional wear and tear and exhaustion, cognitive inattention, effort, expecting problems, multitasking and workload, and emotional experiences (eg, anger, irritability, stress, and concern about well-being). An additional 14 studies that evaluated behavioral, emotional, and cognitive impacts without focusing on fatigue found high user ratings on data quality, accuracy, and processing but low satisfaction with clerical tasks, the effort required in work, and interruptions costing time, resulting in more errors, stress, and frustration. Our qualitative analysis suggests a spectrum from health to risk and provides an outline of organizational approaches to human factors and technology in health care. Business, occupational health, human factors, and well-being literature have not studied technology fatigue and burnout; however, their findings help contextualize technology-based fatigue to suggest guidelines. Few studies were found to contextually evaluate differences according to health professions and practice contexts. CONCLUSIONS: Health care systems need to evaluate the impact of technology in accordance with the Quadruple Aim to support providers' well-being and prevent workload burden, fatigue, and burnout. Implementation and effectiveness approaches and a multilevel approach with objective measures for clinical, human factors, training, professional development, and administrative workflow are suggested. This requires institutional strategies and competencies to integrate health care quality, technology and well-being outcomes.

Primary Care Physician Adherence to Telepsychiatry Recommendations: Intermediate Outcomes from a Randomized Clinical Trial.

Objective:To compare clinical recommendations given by psychiatrists and the adherence to these recommendations by primary care physicians (PCP) following consultations conducted by asynchronous telepsychiatry (ATP) and synchronous telepsychiatry (STP).Materials and Methods:ATP and STP consultations were compared using intermediate data from a randomized clinical trial with adult participant enrollment between April 2014 and December 2017. In both study arms, PCPs received written recommendations from the psychiatrist after each encounter. Independent clinicians reviewed PCP documentation to measure adherence to those recommendations in the 6 months following the baseline consultation.Results:Medical records were reviewed for 645 psychiatrists' consult recommendations; 344 from 61 ATP consultations and 301 from 62 STP consultations. Of those recommendations, 191 (56%) and 173 (58%) were rated fully adherent by two independent raters for ATP and STP, respectively. In a multilevel ordinal logistic regression model adjusted for recommendation type and recommended implementation timing, there was no statistically significant difference in adherence to recommendations for ATP compared with STP (adjusted odds ratio = 0.91, 95% confidence interval = 0.51-1.62). The profiles of recommendation type were comparable between ATP and STP.Conclusions:This is the first PCP adherence study comparing two forms of telemedicine. Although we did not find evidence of a difference between ATP and STP; this study supports the feasibility and acceptability of ATP and STP for the provision of collaborative psychiatric care. Clinical Trial Identifier NCT02084979.

Measurable residual disease monitoring provides insufficient lead-time to prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia.

Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and the fusion proteins RUNX1-RUNX1T1 and CBFB-MYH11. International guidelines recommend monitoring for measurable residual disease every 3 months for 2 years after treatment. However, it is unknown if serial molecular monitoring can predict and prevent morphologic relapse. We conducted a retrospective single-center study of 114 patients in complete remission who underwent molecular monitoring with RT-qPCR of RUNX1-RUNX1T1 or CBFB-MYH11 transcripts every 3 months. Morphologic relapse was defined as re-emergence of >5% blasts and molecular relapse as ≥1 log increase in transcript level between 2 samples. Over a median follow-up time of 3.7 years (range 0.2-14.3), remission persisted in 71 (62.3%) patients but 43 (37.7%) developed molecular or morphologic relapse. Patients who achieved <3 log reduction in RUNX1-RUNX1T1 or CBFB-MYH11 transcripts at end of chemotherapy had a significantly higher risk of relapse compared to patients who achieved ≥3 log reduction (61.1% vs. 33.7%, p=0.004). The majority of relapses (74.4%, n=32) were not predicted by molecular monitoring and occurred rapidly with <100 days from molecular to morphologic relapse. Molecular monitoring enabled the detection of impending relapse and permitted pre-emptive intervention prior to morphologic relapse in only 11 (25.6%) patients. The current practice of molecular monitoring every 3 months provided insufficient lead-time to identify molecular relapses and prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia treated at our institution. Further research is necessary to determine the optimal monitoring strategies for these patients.

Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes.

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius-Clapeyron (CC) rate (6-7% K-1), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

Clinical Outcomes of Asynchronous Versus Synchronous Telepsychiatry in Primary Care: Randomized Controlled Trial.

BACKGROUND: Asynchronous telepsychiatry (ATP; delayed-time) consultations are a novel form of psychiatric consultation in primary care settings. Longitudinal studies comparing clinical outcomes for ATP with synchronous telepsychiatry (STP) are lacking. OBJECTIVE: This study aims to determine the effectiveness of ATP in improving clinical outcomes in English- and Spanish-speaking primary care patients compared with STP, the telepsychiatry usual care method. METHODS: Overall, 36 primary care physicians from 3 primary care clinics referred a heterogeneous sample of 401 treatment-seeking adult patients with nonurgent psychiatric disorders. A total of 184 (94 ATP and 90 STP) English- and Spanish-speaking participants (36/184, 19.6% Hispanic) were enrolled and randomized, and 160 (80 ATP and 80 STP) of them completed baseline evaluations. Patients were treated by their primary care physicians using a collaborative care model in consultation with the University of California Davis Health telepsychiatrists, who consulted with patients every 6 months for up to 2 years using ATP or STP. Primary outcomes (the clinician-rated Clinical Global Impressions [CGI] scale and the Global Assessment of Functioning [GAF]) and secondary outcomes (patients' self-reported physical and mental health and depression) outcomes were assessed every 6 months. RESULTS: For clinician-rated primary outcomes, ATP did not promote greater improvement than STP at 6-month follow-up (ATP vs STP, adjusted difference in follow-up at 6 months vs baseline differences for CGI: 0.2, 95% CI -0.2 to 0.6; P=.28; and GAF: -0.6, 95% CI -3.1 to 1.9; P=.66) or 12-month follow-up (ATP vs STP, adjusted difference in follow-up at 12 months vs baseline differences for CGI: 0.4, 95% CI -0.04 to 0.8; P=.07; and GAF: -0.5, 95% CI -3.3 to 2.2; P=.70), but patients in both arms had statistically and clinically significant improvements in both outcomes. There were no significant differences in improvement from baseline between ATP and STP on any patient self-reported ratings at any follow-up (all P values were between .17 and .96). Dropout rates were higher than predicted but similar between the 2 arms. Of those with baseline visits, 46.8% (75/160) did not have a follow-up at 1 year, and 72.7% (107/147) did not have a follow-up at 2 years. No serious adverse events were associated with the intervention. CONCLUSIONS: This is the first longitudinal study to demonstrate that ATP can improve clinical outcomes in English- and Spanish-speaking primary care patients. Although we did not find evidence that ATP is superior to STP in improving clinical outcomes, it is potentially a key part of stepped mental health interventions available in primary care. ATP presents a possible solution to the workforce shortage of psychiatrists and a strategy for improving existing systems of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.

The Medical Resuscitation Committee: Interprofessional Program Development to Optimize Care for Critically Ill Medical Patients in an Academic Pediatric Emergency Department.

ABSTRACT: Provision of optimal care to critically ill patients in a pediatric emergency department is challenging. Specific challenges include the following: (a) patient presentations are highly variable, representing the full breadth of human disease and injury, and are often unannounced; (b) care team members have highly variable experience and skills and often few meaningful opportunities to practice care delivery as a team; (c) valid data collection, for quality assurance/improvement and clinical research, is limited when relying on traditional approaches such as medical record review or self-report; (d) specific patient presentations are relatively uncommon for individual providers, providing few opportunities to establish and refine the requisite knowledge and skill; and (e) unscientific or random variation in care delivery. In the current report, we describe our efforts for the last decade to address these challenges and optimize care delivery to critically ill patients in a pediatric emergency department. We specifically describe the grassroots development of an interprofessional medical resuscitation program. Key components of the program are as follows: (a) a database of all medical patients undergoing evaluation in the resuscitation suite, (b) peer review and education through video-based case review, (c) a program of emergency department in situ simulation, and (d) the development of cognitive aids for high-acuity, low-frequency medical emergencies.

A Literature Review Comparing Clinicians' Approaches and Skills to In-Person, Synchronous, and Asynchronous Care: Moving Toward Competencies to Ensure Quality Care.

Introduction: Research is increasing on asynchronous technologies used by specialist clinicians and primary care, including e-mail, text, e-consultation, and store-and-forward (asynchronous) options. Studies typically describe interventions and care outcomes rather than development of clinical skills for using technology. Methods: This article attempts to compare clinicians' approaches to, and skills for, asynchronous technologies versus in-person and synchronous (i.e., video) care. Literature from technology, health care, pedagogy, and business were searched from 2000 to 2019 for title words, including synchronous (e.g., video, telemental or behavioral health, telepsychiatry), asynchronous (e.g., app, e-consultation, e-mail, text, sensor in a wearable device), education, clinical, and consultation. Results: From a total of 4,812 potential references, two authors (D.M.H., J.T.) found 4,622 eligible for full text review and found 381 articles directly relevant to the concept areas in combination for full text review. However, exclusion criteria subtracted 305, leaving a total of 76 articles. While in-person and synchronous care are similar in many ways, the clinical approach to asynchronous care has many differences. As asynchronous technologies and models of care are feasible and effective, often for consultation, an outline of patient, primary care provider, and specialist clinician goals and skills are presented. Few studies specifically discuss skills or competencies for asynchronous care, but components from published clinical informatics, video, social media, and mobile health competencies were organized into Accreditation Council of Graduate Medical Education domains. Conclusions: Further implementation of science research is needed for asynchronous technology interventions, as well as clinician competencies using asynchronous technologies, to ensure optimal outcomes for patients in health care.

Asynchronous Telepsychiatry Interviewer Training Recommendations: A Model for Interdisciplinary, Integrated Behavioral Health Care.

Objective: Asynchronous telepsychiatry (ATP) is an integrative model of behavioral health service delivery that is applicable in a variety of settings and populations, particularly consultation in primary care. This article outlines the development of a training model for ATP clinician skills. Methods: Clinical and procedural training for ATP clinicians (n = 5) was provided by master's-level, clinical mental health providers developed by three experienced telepsychiatrists (P.Y. D.H., and J.S) and supervised by a tele-psychiatrist (PY, GX, DL) through seminar, case supervision, and case discussions. A training manual and one-on-one sessions were employed for initial training. Unstructured expert discussion and feedback sessions were conducted in the training phase of the study in year 1 and annually thereafter over the remaining 4 years of the study. The notes gathered during those sessions were synthesized into themes to gain a summary of the study telepsychiatrist training recommendations for ATP interviewers. Results: Expert feedback and discussion revealed three overarching themes of recommended skill sets for ATP interviewers: (1) comprehensive skills in brief psychiatric interviewing, (2) adequate knowledge base of behavioral health conditions and therapeutic techniques, and (3) clinical documentation, integrated care/consultation practices, and e-competency skill sets. The model of training and skill requirements from expert feedback sessions included these three skill sets. Technology training recommendations were also identified and included: (1) awareness of privacy/confidentiality for electronic data gathering, storage, management, and sharing; (2) technology troubleshooting; and (3) video filming/retrieval. Conclusions: We describe and provide a suggested training model for the use of ATP integrated behavioral health. The training needs for ATP clinicians were assessed on a limited convenience sample of experts and clinicians, and more rigorous studies of training for ATP and other technology-focused, behavioral health services are needed. Clinical Trials number: NCT03538860.

Anticoagulation prophylaxis reduces venous thromboembolism rate in adult acute lymphoblastic leukaemia treated with asparaginase-based therapy.

Venous thromboembolism (VTE) is a well-known complication in adults receiving asparaginase (ASNase)-based intensification chemotherapy for acute lymphoblastic leukaemia (ALL). The optimal preventative strategy is unclear. Our objective is to determine the effects of low-molecular-weight heparin (LMWH) as primary VTE prophylaxis. A single-centred retrospective cohort study of adult patients with Philadelphia chromosome negative (Ph-) ALL who received ASNase-based intensification from 2001 to 2017, with prophylaxis given from 2011 to 2017. In all, 214 patients were included in this study with 99 in the historical control group and 125 in the prophylaxis group. The mean (range) enoxaparin dose was 0·79 (0·39-1·2) mg/kg. Of the 125 patients in the prophylaxis group 17 (13·6%) developed VTE during the intensification phase, while 27/99 patients (27·3%) in the control cohort experienced at least one thrombotic event (odds ratio [OR] 0·42, 95% confidence interval [CI] 0·21-0·83). Overall, the main sites of VTE incidences included deep vein thrombosis in the lower extremity (54·6%), pulmonary embolism (13·6%) and catheter-related thrombosis (22·7%). In addition, we found that after adjusting for age, T-phenotype ALL was associated with VTE development (OR 3·07, 95% CI 1·04-9·08). There was no documented major bleeding in the prophylaxis group. LMWH prophylaxis reduced the incidence of symptomatic VTE in adult patients with ALL receiving intensification chemotherapy with ASNase.

Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia.

Optimization of post-remission therapies to maintain complete remission and prevent relapse is a major challenge in treating patients with acute myeloid leukemia (AML). Monitoring patients for measurable residual disease (MRD) is helpful to identify those at risk for relapse. Hypomethylating agents are being investigated as post-remission therapy. Identification of recurrent genetic alterations that drive disease progression has enabled the design of new, personalized approaches to therapy for patients with AML. Emerging data suggest that targeted post-remission therapy, alone or in combination with chemotherapy, may improve outcomes. Results of ongoing clinical trials will further define potential clinical benefits.

Computer-Assisted Cognitive-Behavior Therapy and Mobile Apps for Depression and Anxiety.

PURPOSE OF REVIEW: We reviewed research on computer-assisted cognitive-behavior therapy (CCBT) and mobile applications with the goals of assessing the effectiveness of these newer methods of delivering or augmenting treatment and making recommendations on the clinical use of computer tools in psychotherapy of depression and anxiety. RECENT FINDINGS: Research on CCBT has found solid evidence for efficacy when the use of a therapeutic computer program is supported by a clinician or other helping professionals. Lower levels of efficacy or ineffectiveness typically have been found when computer programs are used as stand-alone treatments. A large number of mobile apps have been created that claim to be useful for depression and/or anxiety. However, considerable caution is warranted in evaluating mobile apps and recommending them to patients. Research on mobile apps is still in an early stage of development. A number of well-established CCBT programs have been studied in multiple randomized, controlled trials and have been found to be effective. Such programs appear to have adequate quality, security, and efficacy to be used in clinical practice. Mobile apps offer easy portability and immediate access to coping strategies and may be useful for augmenting treatment. But clinicians need to select apps with integrity and reliable content for clinical use.