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Background. The Coronavirus disease 2019 (COVID-19) pandemic negatively impacted nursing students' opportunity to gain experience through clinical placement, potentially threatening their readiness for practice and their clinical competence. The aim of this study was to explore whether and to what extent the thirdyear undergraduate nursing students perceived that their readiness for practice was impacted by changes to clinical placement and classroom learning implemented in response to the COVID-19 pandemic. Study design. Cross-sectional study. Methods. The study was conducted in a university of North-western Italy that provides nursing education across five sites. All sites stopped in-person classroom learning at the beginning of March 2020, but each site was free to decide whether to continue in-person clinical placement based on the local epidemiological situation. All 228 third-year nursing students who completed their degree by June 2020 were invited to participate. Data were collected via online questionnaire, which included the question "What impact do you think that COVID-19 safety measures employed by your nursing programme had on your readiness for practice?" Answers were given on a 5-point Likert scale (none, minimal, moderate, major, and severe). Explanatory variables were collected at the individual, nursing programme, and university site levels. Results. A total of 126 (response rate 55.3%) nursing students completed the questionnaire. Overall, 84 (66.7%) perceived that COVID-19 safety measures had a moderate to severe impact on their readiness for practice. These students often had lower grade point averages (p=0.037) and received no clinical placement during the pandemic (72.6% vs 90.5% of students who reported no or minimal impact, p=0.022). Average duration of third-year clinical placement was also lower among these students, though it was not statistically significant. No differences emerged at the university site level. Conclusions. Despite important advances in technology-based educational activities, clinical placement remains the best educational strategy to allow nursing students to feel prepared to work effectively during a pandemic. [ABSTRACT FROM AUTHOR]

Post-transplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GvHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear.We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into four groups: Group I (CNI + MTX or MMF), Group II (CNI + MTX or MMF + ATG), Group III (PTCy + ATG + CNI), and Group IV (PTCy + CNI + MMF). PTCy was associated with a significant reduction in grade II-IV [HR 0.6, p=0.01] and grade III-IV acute GvHD [HR 0.2, p=0.001] as well as all grade chronic GvHD [HR 0.5, p=0.007] and moderate-severe chronic GvHD [HR 0.4, p=0.001] compared to CNI+MTX (or MMF) containing regimens. PTCy did not increase relapse risk; PTCy reduced NRM [HR 0.3, p<0.002], leading to improved GvHD-free/relapse-free survival (GRFS) [HR 0.4, p<0.001]. PTCy was also associated with improved overall survival [HR 0.56, p=0.01]. Bloodstream infections are increased with PTCy [HR: 1.5, p=0.001]. The addition of ATG to PTCy did not further improve the GRFS and was associated with a higher incidence of clinically significant Cytomegalovirus (CMV) [HR 2.16, p=0.002] and Epstein-Barr virus reactivation (EBV) [HR 9.5, p<0.001] and a numerical increase in NRM [HR 1.7, p=0.2]. PTCy significantly appeared to improve GRFS in the MSD setting using PBSC grafts. The addition of ATG to PTCy increases csCMV and csEBV reactivation without further improving GRFS. Prospective trials and PTCy dose optimization are warranted., (Copyright © 2024 American Society of Hematology.)

Objective: To synthesize evidence assessing the effectiveness of quality improvement (QI) interventions in reducing hospital service use from nursing homes (NHs)., Design: Systematic review and meta-analysis of randomized controlled trials (RCTs), controlled before-after (CBA), uncontrolled before-after (UBA), and interrupted time series studies. Searches were conducted in MEDLINE, CINAHL, The Cochrane Library, Embase, and Web of Science from 2000 to August 2023 (PROSPERO: CRD42022364195)., Setting and Participants: Long-stay NH residents (>30 days)., Methods: Included QI interventions using a continuous and data-driven approach to assess solutions aimed at reducing hospital service use. Risk of bias was assessed using JBI tools. Delivery arrangements and implementation strategies were categorized through EPOC taxonomy., Results: Screening of 14,076 records led to the inclusion of 22 studies describing 29 QI interventions from 6 countries across 964 NHs. Ten studies, comprising 4 of 5 RCTs, 3 of 4 CBAs, and 1 of 12 UBAs were deemed to have a low risk of bias. All but 3 QI interventions used multiple component delivery arrangements (median 6; IQR 3-8), focusing on the "coordination of care and management of care processes" alone or combined with "changes in how, when, where, and by whom health care is delivered." The most frequently used implementation strategies were educational meetings (n = 25) and materials (n = 20). The meta-analysis of 11 studies showed a significant reduction in "all-cause hospital admissions" for QI interventions compared with standard care (rate ratio, 0.60; 95% CI, 0.41-0.87; I 2  = 99.3%), with heterogeneity due to study design, QI intervention duration, type of delivery arrangements, and number of implementation strategies. No significant effects were found for emergency department (ED) visits or potentially avoidable hospitalizations., Conclusions and Implications: The study provides preliminary evidence supporting the implementation of QI interventions seeking to reduce hospital admissions from NHs. However, these findings require confirmation through future experimental research., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Our objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM)., Design: Retrospective cohort study (2014-2022)., Setting: Medic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center., Patients: Adult patients admitted to ICU with a concomitant diagnosis of a hematological malignancy., Interventions: None., Main Variables of Interest: We analyzed demographic data, use of thromboprophylaxis and secondary outcomes that included incidence of VTE (venous thromboembolism), bleeding, mortality, severity scores and organ support. We applied a multivariable logistic regression model to examine the risk of thrombosis in the ICU., Results: We included 862 ICU admissions (813 unique patients). Thromboprophylaxis was given during 65% of admissions (LMWH 14%, UFH 8%, and SCDs 43%); in 21% it was contraindicated due to thrombocytopenia; 14% of cases lacked documentation on prophylaxis. There were 38 unique incident cases of VTE (27 DVT, 11 PE), constituting 4.4% of ICU episodes. Most of VTE cases happened in patients with various degrees of thrombocytopenia. In the multivariable analysis, SOFA score on the first ICU day was independently associated (OR 0.85, 95% CI 0.76-0.96) with the risk of VTE. Bleeding occurred in 7.2% (minor) and 14.4% (major) of episodes; most frequent sites being CNS, abdomen/GI and pulmonary., Conclusions: In this cohort of critically ill patients with HM, there was considerable variability in the utilization of DVT prophylaxis, with predominant use of SCDs. The incidence of VTE was 4.4% and major bleeding 14%., Clinical Trial Registration: NCT05396157. Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study (https://clinicaltrials.gov/)., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Letermovir, a novel anti-cytomegalovirus (CMV) agent acts by inhibiting the viral terminase complex and is approved for primary prophylaxis in CMV seropositive patients post allogeneic hematopoietic cell transplantation (HCT). The favorable efficacy and safety profile make it an attractive option for use as secondary prophylaxis in patients at high-risk for CMV reactivation. In this study, we report the efficacy and safety of letermovir secondary prophylaxis after at least one treated episode of CMV reactivation in a cohort of 39 high-risk patients. Thirty two (82%) patients received anti-thymocyte globulin (ATG), 27 (69%) received a combination of ATG and post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis. Twenty one patients (54%) received CMV seronegative grafts. In addition, 18 (46%) patients had HLA mismatched unrelated or haploidentical donors while 18 (46%) had active GVHD requiring immunosuppression at the time of commencing secondary prophylaxis. Letermovir was initiated at a median of 47 days (range, 41-56) after HCT and was administered for a median duration of 77 days (range, 46-90). A single breakthrough CMV reactivation was noted in this high-risk cohort. Four additional episodes of CMV reactivation occurred at a median of 28 days (range, 23-59 days) after discontinuation of secondary prophylaxis. The drug was well tolerated and 77% of the cohort completed the planned duration of secondary prophylaxis. None of the patients discontinued treatment due to treatment-related adverse effects. In conclusion, letermovir is effective and well tolerated and may be considered for secondary prophylaxis in patients at high risk for CMV reactivation. Prospective studies are required to validate these findings., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cytomegalovirus (CMV) reactivation post-allogeneic hematopoietic cell transplantation (post-alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre-alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis. CMV serology was assessed at consult and pretransplant. The cohort was divided into four groups based on pretransplant CMV seroconversion: negative to positive (Group 1), positive to negative (Group 2), consistently negative (Group 3), and consistently positive (Group 4). Eighty-nine patients (12%) had seroconverted from negative to positive, 17 (2%) from positive to negative, 151 (20%) were consistently seronegative, and 495 (66%) were consistently seropositive pretransplant. For the four CMV serostatus groups, cumulative incidence of CMV reactivation at 6 months posttransplant was 4.5%, 47.1%, 6.6%, and 76.6% for Groups 1, 2, 3, and 4, respectively (p < .0001). No differences between groups were seen regarding Grade III-IV acute graft-versus-host disease (GVHD) (p = .91), moderate/severe chronic GVHD (p = .41), or graft failure (p = .28). On multivariable analysis, there was no impact of CMV serostatus group on overall survival (p = .67), cumulative incidence of relapse (p = .83) or non-relapse mortality. alloHCT patients who demonstrate CMV seroconversion pretransplant from negative to positive have a very low risk of CMV reactivation posttransplant. The observed seroconversion may be due to passive CMV immunity acquired through blood products. Quantitative CMV immunoglobulin G/immunoglobulin M pretransplant may help differentiate between true seroconversion and passively transmitted CMV immunoglobulin., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia at Princess Margaret Hospital, Toronto, from 2015 to 2022. Using propensity score matching, we compared transplant outcomes between 2 well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n = 46) or fludarabine-busulfan with total body irradiation (FBT200) (n = 92). A scoring system based on patient age, Karnofsky performance score, and hematopoietic cell transplant comorbidity index was used to assign patients based on fitness to low-dose (30 g/m 2 ) or high-dose (42 g/m 2 ) treosulfan: 32 (69.6%) received high-dose treosulfan. The racial composition of the 2 groups was similar, with 27.2% and 21.7% of FBT200 and FT recipients, respectively, identifying as non-Caucasian (P = .61). Primary outcomes were analyzed at a median follow-up of 747 days. Of all participants, 116 (84.0%) received graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCY) and antithymocyte globulin (ATG). Patients who received FT had a superior 2-year overall survival (OS) compared to those who received FBT200: 66.9% (95% confidence interval (CI): 46.1 to 81.2) versus 44.5% (95% CI: 34 to 54.4), hazard ratio (HR): 0.43, 95% CI: 0.22 to 0.84 (P = .013). In multivariate analysis (MVA), only the use of fresh grafts (P = .02) and FT (P = .01) were associated with improved OS. FT was associated with superior 2-year relapse-free survival (RFS) compared to FBT200: 63.1% (95% CI: 42.6 to 77.9) versus 39.1% (95% CI: 29.1 to 49.1), HR: 0.44 (95% CI: 0.24 to 0.81), P = .008. In MVA, the use of fresh grafts (P = .03) and FT (P = .009) were associated with improved RFS. Recipients of FT demonstrated superior 2-year graft-versus-host disease relapse-free survival (GRFS) compared to those who received FBT200: 57.4% (95% CI: 37.8 to 72.8) versus 35.1% (95% CI: 25.5 to 45). In MVA, only FT was associated with superior GRFS (P = .02). FT recipients exhibited markedly superior 1-year event-free survival compared to recipients of FBT200 in univariate analysis (40.3% (95% CI: 25.9 to 54.2) versus 9.2% (95% CI: 4.4 to 16.3), HR: 0.47 (95% CI: 0.30 to 0.72), P < .001) and MVA (P = .004). FT was associated with lower 1-year nonrelapse mortality compared to FBT200 in univariate analysis (9.9% (95% CI: 3.0 to 21.8) versus 29.7% (95% CI: 20.6 to 39.3), HR: 0.41 (95% CI: 0.17 to 0.96), P = .04) and MVA (P = .04). Our study utilized propensity score matching to demonstrate superiority of treosulfan- over busulfan-based conditioning in stem cell transplantation of patients with MDS and is the first to evaluate the performance of treosulfan-based conditioning in combination with ATG and PTCY. As such, it contributes to the increasing body of evidence supporting the safety of treosulfan, even at the dose of 42 g/m 2 ., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Poor treatment adherence and lack of self-care behaviors are significant contributors to hospital readmissions of people with heart failure (HF). A transitional program with non-invasive telemonitoring may help sustain patients and their caregivers to timely recognize signs and symptoms of exacerbation. We will conduct a Randomized Clinical Trial (RCT) to evaluate the feasibility and acceptability of a 6-month supportive intervention for patients discharged home after cardiac decompensation. Forty-five people aged 65 years and over will be randomized to either receive a supportive intervention in addition to standard care, which combines nurse-led telephone coaching and a home-based self-monitoring vital signs program, or standard care alone. Four aspects of the feasibility will be assessed using a mixed-methods approach: process outcomes (e.g., recruitment rate), resources required (e.g., adherence to the intervention), management data (e.g., completeness of data collection), and scientific value (e.g. 90- and 180-day all-cause and HF-related readmissions, self-care capacity, quality of life, psychological well-being, mortality, etc.). Participants will be interviewed to explore preferences and satisfaction with the intervention. The study is expected to provide valuable insight into the design of a definitive RCT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Acute graft versus host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplant (HCT) and is associated with significant morbidity and mortality. Steroid refractory aGVHD (SR-aGVHD) carries a particularly grim prognosis. Ruxolitinib has shown promise for treatment of SR-aGVHD in a phase 3 trial; however, safety and efficacy data outside of the clinical trial setting is lacking. We performed a multicenter retrospective study to examine the response to ruxolitinib and its efficacy in patients with SR-aGVHD. We included 59 patients treated with ruxolitinib for SR-aGVHD between 2015 and 2022. Of these 59 patients, 36 patients (61.0%) achieved a complete (CR) or partial response (PR) at 28 days, while 31 patients (52.5%) obtained a CR/PR at day 56. Patients that achieved a CR or PR at day 28 had a higher rate of overall survival (OS; 69.2%), compared with patients that did not (31.6%; p = 0.037). OS at 12 months was 41.5%, with a median OS duration of 5.3 months. Failure free survival (FFS) at 12 months was 29.1%, with a median FFS of 2.6 months. Overall, this real-world experience data support ruxolitinib as the standard of care for SR-aGVHD in a non-controlled trial population., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In 2015, dual T cell depletion with antithymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) combined with cyclosporine A (CsA) replaced our prior institutional graft-versus-host disease (GVHD) prophylaxis regimen of 4.5 mg/kg ATG, CsA, and mycophenolate mofetil (MMF) (ATG-based) in 10/10 HLA-matched unrelated donor (MUD) peripheral blood allogeneic hematopoietic stem cell transplantation (allo-HCT). The initial ATG dose of 4.5 mg/kg [ATG(4.5)/PTCy] was reduced to 2 mg/kg [ATG(2)/PTCy] in 2018. This study compares the results obtained from 444 adults undergoing MUD allo-HCT at our institution who received ATG(4.5)/PTCy (n = 127) or ATG(2)/PTCy (n = 223) with those who received ATG-based prophylaxis without PTCy (n = 84). The rates of grade II-IV and grade III-IV acute GVHD (aGVHD) at day +100 and moderate/severe chronic GVHD (cGVHD) at 1 year were 35.7%, 21.6%, and 14.7%, respectively, in patients receiving ATG-based prophylaxis without PTCy; 16.5%, 4.9%, and 4.3% in patients receiving ATG(4.5)/PTCy; and 23.3% (P = .004), 8.0% (P < .001), and 14.1% (P =.006) in patients receiving ATG(2)/PTCy. One-year overall survival (OS), nonrelapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) were 69.8%, 25.3%, and 52.0%, respectively, for patients receiving ATG-based prophylaxis without PTCy; 82.7%, 17.3%, and 59.8% for patients receiving ATG(4.5)/PTCy; and 78.3% (P = .446), 14.7% (P = 101), and 56.2% (P = .448) for patients receiving ATG(2)/PTCy. On univariate analyses, the use of ATG(2)/PTCy was associated with a lower risk of NRM (hazard ratio, .54; P = .023) compared with the use of ATG-based prophylaxis without PTCy. ATG(2)/PTCy prophylaxis effectively prevents GVHD and is associated with comparable relapse risk, OS, and GRFS as seen with ATG(4.5)/PTCy and ATG-based prophylaxis without PTCy., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Blinatumomab, a bispecific monoclonal antibody, effectively controls refractory B cell acute lymphoblastic leukemia (ALL) and promotes measurable residual disease (MRD) negativity. This study investigated the impact of pretransplant blinatumomab on allogeneic hematopoietic cell transplantation (HCT) outcomes in B cell ALL patients., Methods: We analyzed the effect of pretransplant blinatumomab on transplant outcomes of 117 adults undergoing allogeneic HCT for B cell ALL at Princess Margaret Hospital, Toronto, between 2010 and 2021. Outcomes assessed included overall survival (OS), graft-versus-host disease and relapse-free survival (GRFS), cumulative incidences of relapse (CIR), and nonrelapse mortality (NRM)., Results: The median follow-up was 36 months. Thirty-one participants (26.5%) received blinatumomab. Blinatumomab group had higher proportions of individuals with high disease risk index, primary induction failure and was more likely to receive dual T cell depletion with antithymocyte globulin and post-transplant cyclophosphamide. Two-year OS, GRFS, NRM, and CIR in the blinatumomab and nonblinatumomab groups were, respectively: 65.4% versus 45.6% (P = .05), 42.2% versus 17.3% (P = .01), 3.2% versus 43.0% (P = .007) and 34.4% versus 14.4% (P = .02). Blinatumomab was associated with a lower incidence of day-100 grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD): 27.5% versus 56.7% (P = .009), and 10.9% versus 34.7% (P = .04), respectively. Multivariate analysis confirmed the association between pretransplant blinatumomab and improved OS and NRM., Conclusions: Pretransplant blinatumomab is associated with improved OS and lower risk of NRM in B cell ALL patients undergoing allogeneic HCT, likely reflecting lower burden of treatment-related toxicity in this population. Larger prospective trials are warranted to validate our findings., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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 (MRD pos ) post-induction. MRD pos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRD neg 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 MRD pos 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 MRD pos intermediate-risk AML patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)