Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation.

We report the results of a Phase I radiation dose escalation study using an yttrium-90 (90Y) labelled anti-CD66 monoclonal antibody given with standard conditioning regimen for patients receiving haematopoietic stem cell transplants for myeloid leukaemia or myeloma. The 90Y-labelled anti-CD66 was infused prior to standard conditioning. In total, 30 patients entered the trial and 29 received 90Y-labelled mAb, at infused radiation activity levels of 5, 10, 25, or 37.5 megaBequerel (MBq)/kg lean body weight. A prerequisite for receiving the 90Y-labelled mAb was favourable dosimetry determined by single-photon emission computerised tomography (SPECT) dosimetry following administration of indium-111 (111In) anti-CD66. Estimated absorbed radiation doses delivered to the red marrow demonstrated a linear relationship with the infused activity of 90Y-labelled mAb. At the highest activity level of 37.5 MBq/kg, mean estimated radiation doses for red marrow, liver, spleen, kidneys and lungs were 24.6 ± 5.6 Gy, 5.8 ± 2.7 Gy, 19.1 ± 8.0 Gy, 2.1 ± 1.1 and 2.2 ± 0.9, respectively. All patients engrafted, treatment-related mortality 1-year post-transplant was zero. Toxicities were no greater than those anticipated for similar conditioning regimens without targeted radiation. The ability to substantially intensify conditioning prior to haematopoietic stem cell transplantation without increasing toxicity warrants further testing to determine efficacy. clinicaltrials.gov identifier: NCT01521611.

Allogeneic hematopoietic stem-cell transplantation for patients with Richter transformation: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Management of Richter transformation (RT) is particularly challenging, with survival estimates <1 year. We report on outcomes of 66 RT patients undergoing allogeneic-HCT (allo-HCT) between 2008 and 2018 registered with the EBMT. Median age at allo-HCT was 56.2 years (interquartile range (IQR), 51.3-63.1). Median time from RT to allo-HCT was 6.9 months (IQR, 4.9-11) and 28 (42.4%) were in complete remission (CR). The majority underwent reduced intensity conditioning (66.2%) using peripheral blood derived stem cells. Eighteen (27.3%) patients had a matched sibling donor, 24 (36.4%) a matched unrelated donor and the remaining were mismatched. Median follow-up was 6.6 years; 1- and 3- year overall and progression free survival (PFS) (95% CI) was 65% (54-77) and 39% (27-51) and 53% (41-65) and 29% (18-40), respectively. Patients in CR at time of allo-HCT had significantly better 3-year PFS (39% vs. 21%, p = 0.032). Cumulative incidences of grade II-IV acute graft versus host disease (GVHD) at day +100 was 41% (95% CI 29-53) and chronic GVHD at 3 years was 53% (95% CI 41-65). High rates of non-relapse mortality (NRM) were observed; 38% (95% CI, 26-50) at 3 years. Although potentially curative, approaches to reduce considerable NRM and chronic GVHD rates are required.

Venetoclax-based low intensity therapy in molecular failure of NPM1-mutated AML.

ABSTRACT: Molecular failure in NPM1-mutated acute myeloid leukemia (AML) inevitably progresses to frank relapse if untreated. Recently published small case series show that venetoclax combined with low-dose cytarabine or azacitidine can reduce or eliminate measurable residual disease (MRD). Here, we report on an international multicenter cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (≥1-log reduction in MRD) in 66 patients (84%) and MRD negativity in 56 (71%). Eighteen of 79 patients (23%) required hospitalization, and no deaths were reported during treatment. Forty-one patients were bridged to allogeneic transplant with no further therapy, and 25 of 41 were MRD negative assessed by reverse transcription quantitative polymerase chain reaction before transplant. Overall survival (OS) for the whole cohort at 2 years was 67%, event-free survival (EFS) was 45%, and in responding patients, there was no difference in survival in those who received a transplant using time-dependent analysis. Presence of FLT3-ITD mutation was associated with a lower response rate (64 vs 91%; P < .01), worse OS (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.06-5.86; P = .036), and EFS (HR, 1.87; 95% CI, 1.06-3.28; P = .03). Eighteen of 35 patients who did not undergo transplant became MRD negative and stopped treatment after a median of 10 months, with 2-year molecular relapse free survival of 62% from the end of treatment. Venetoclax-based low intensive chemotherapy is a potentially effective treatment for molecular relapse in NPM1-mutated AML, either as a bridge to transplant or as definitive therapy.

Treatment Integrity Reporting in Behavior Analysis in Practice 2008-2019.

Treatment integrity is the extent to which procedures are implemented in a manner consistent with their prescribed protocols and is necessary for reaching accurate conclusions regarding functional relations between dependent (i.e., behavior) and independent (i.e., the environment) variables. Several studies assessing the frequency that studies report treatment integrity have been conducted. However, no review has included articles from Behavior Analysis in Practice. Thus, the current study reviewed Behavior Analysis in Practice between 2008 and 2019 to assess the frequency of studies reporting treatment integrity data. A total of 193 articles consisting of 205 studies met the inclusionary criteria for this review. Ninety-six studies (46.83%) reported treatment integrity data, compared to 193 (94.15%) that provided interobserver agreement data. Additionally, 98 studies (47.80%) were considered high risk for treatment implementation inaccuracies. Recommendations and implications for research and practice are discussed.

The Lived Experience of DACA Recipients Who Are US Nursing Program Graduates and Their Pathways to Professional Licensure: A Phenomenological Study.

AIM: This phenomenological study explored the experiences of Deferred Action for Childhood Arrivals (DACA) recipients who are nursing program graduates in the United States and their pathways to professional licensure. BACKGROUND: DACA is a federal program facilitating lawful employment and higher education to qualified US immigrants. Understanding the experience of DACA recipients who have become registered nurses will inform nurse educators' advocacy to create a more diverse nursing workforce. METHOD: DACA recipients ( n = 17) who were US nursing program graduates were interviewed to explore the phenomenon of a pathway to professional licensure. RESULTS: The pathway to professional licensure emerged within four themes: pursuing the dream, finding support, figuring it out, and advocating for others. CONCLUSION: To contribute to a diverse nursing workforce, the authors recommend that nurse educators advocate for policies to support DACA recipients who graduate from US nursing programs to achieve professional nursing licensure.

Declaring Uncertainty: Using Quality Improvement Methods to Change the Conversation of Diagnosis.

BACKGROUND: Diagnostic uncertainty may be a sign that a patient's working diagnosis is incorrect, but literature on proactively identifying diagnostic uncertainty is lacking. Using quality improvement methodologies, we aimed to create a process for identifying patients with uncertain diagnoses (UDs) on a pediatric inpatient unit and communicating about them with the interdisciplinary health care team. METHODS: Plan-do-study-act cycles were focused on interdisciplinary communication, structured handoffs, and integration of diagnostic uncertainty into the electronic medical record. Our definition of UD was as follows: "you wouldn't be surprised if the patient had a different diagnosis that required a change in management." The primary measure, which was tracked on an annotated run chart, was percentage agreement between the charge nurse and primary clinician regarding which patients had a UD. Secondary measures included the percentage of patient days during which patients had UDs. Data were collected 3 times daily by text message polls. RESULTS: Over 13 months, the percentage agreement between the charge nurse and primary clinician about which patients had UDs increased from a baseline of 19% to a median of 84%. On average, patients had UDs during 11% of patient days. CONCLUSIONS: We created a novel and effective process to improve shared recognition of patients with diagnostic uncertainty among the interdisciplinary health care team, which is an important first step in improving care for these patients.

Mindset, Motivation, and Teaching Practice: Psychology Applied to Understanding Teaching and Learning in STEM Disciplines.

Psychological theories of motivation and performance are relevant to teaching and learning in the science, technology, engineering, and mathematics (STEM) disciplines. The present study applies Dweck's mindset theory of motivation to an examination of the relationship among instructor mindset, instructor motivational attitudes, and the use of effective teaching practices. Faculty members who teach undergraduate courses in STEM disciplines completed a survey designed to assess fixed versus growth mindset, mastery orientation (measures of motivation and efficacy), and teaching practices. Results supported a model consistent with Dweck's theory of motivation, whereby mastery orientation mediates the relationship between instructor mindset and teaching behaviors. It appears that this psychological theory of motivation may be helpful in understanding teaching and learning in STEM disciplines. More research using a variety of measures and teaching contexts is necessary before full applicability can be realized.

Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL-class fusion.

Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL-class patients who did and did not receive a TKI in first remission to be compared. ABL-class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009).

Mesenchymal stromal cells for acute graft-versus-host disease: response at 1 week predicts probability of survival.

Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid-resistant graft-versus-host-disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients' overall survival. In our cohort, cell dose, patients' age and type of organ involvement are crucial factors associated with clinical responses.

UK consensus statement on the use of plerixafor to facilitate autologous peripheral blood stem cell collection to support high-dose chemoradiotherapy for patients with malignancy.

Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail. Pre-emptive use has the advantage that it avoids the need to re-schedule the transplant procedure, with its attendant inconvenience, quality-of-life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre-emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl-1 at the time of recovery after chemomobilization or after four days of G-CSF treatment, or an apheresis yield of <1 × 106 CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre-emptive plerixafor.

Measuring health professions students' orientation toward lifelong learning.

OBJECTIVE: Lifelong learning is considered to be an element of professionalism for healthcare professionals. Accreditation standards for health professions educational programs require that lifelong learning be promoted in the curriculae; however, tools to assess whether these standards are met are sparse. This study evaluated the internal structure of student responses on a transdisciplinary adaptation of the Jefferson Scale of Physician Lifelong Learning-Medical Students Version (JeffSPLL-MS). METHODS: The Jefferson Scale of Lifelong Learning-Health Professions Students Version (JeffSPLL-HPS) was administered to 180 students in eight entry-level health professions programs. Confirmatory factor analyses were performed to investigate internal structure. RESULTS: JeffSPLL-MS and JeffSLL-HPS mean scores were similar. Cronbach's alpha for the JeffSLL-HPS was 0.85. Results of the confirmatory factor analysis revealed a three-factor structure of the JeffSLL-HPS that was consistent with that of the JeffSPLL-MS. The Cronbach's alphas for the three factors on the JeffSLL-HPS were 0.78, 0.73, and 0.62. CONCLUSIONS: The JeffSLL-HPS's internal structure is similar to that of the JeffSPLL-MS. The tool may be valuable for faculty and administrators in health professions programs for assessing their goal of meeting accreditation standards and to assess the extent to which their students value the importance of lifelong learning.

Senior student goal setting during subinternship: a mixed-methods study.

BACKGROUND: New developments in Subinternship curricula attempt to establish self-directed learning skills that will translate into the 1st year of residency. However, we know little about how well senior medical students' self-directed learning goals match with what is expected of them in residency. PURPOSES: We designed a mixed-methods study to examine the goals set by senior students at Georgia Health Sciences University on Pediatric Subinternship and to determine how those goals relate to the 6 Accreditation Council for Graduate Medical Education (ACGME) competencies. METHODS: We used an iterative process to categorize self-directed learning goals on Pediatric Subinternships (n=188 goals generated by 57 senior students) by (a) the 6 ACGME competencies and (b) general or specific goals. We used tests of association and multivariate modeling to compare goal categories by clinical site and time of year. RESULTS: There were 56.3% of goals addressing patient care. Professionalism and systems-based practice goals were rare. Of the goals, 72% were general, but goals written by students at the newborn nursery and neonatal intensive care unit sites were significantly more likely to be specific than goals written by students on the general inpatient subinternship. CONCLUSIONS: The overwhelming majority of senior medical student goals on a Pediatric Subinternship are general and related to patient care. Students may need assistance with developing more specific goals in all 6 competencies. Our findings suggest that understanding and incorporating students' learning goals may be important for enhancing the potential effectiveness of transition-to-residence curricula.

Beneficial effects of an arginine-calcium carbonate desensitizing paste for treatment of dentin hypersensitivity.

PURPOSE: To evaluate the clinical efficacy of a single professional application of a Pro-Relief desensitizing fluoride-free paste containing 8% arginine and calcium as compared to a fluoride-free prophylaxis paste on dentin hypersensitivity reduction in adults with a clinical diagnosis of dentin hypersensitivity. METHODS: This single-center, parallel group, double-blind and randomized clinical study conducted in Santo Domingo, Dominican Republic included 50 (25 per group) adult male and female subjects. Each study subject had two teeth hypersensitive to air blast stimuli when applied directly at its cervical surface (gingivo-facial 1/3). An air blast hypersensitivity score equal or greater to 2 (Schiff Cold Air Sensitivity Scale) was randomly assigned to one of two treatment groups (1) Pro-Relief in-office desensitizing fluoride-free paste containing 8% arginine and calcium carbonate (Test Paste group), and (2) a fluoride-free prophylaxis paste (Control Paste group). Prior to their baseline examination, subjects were instructed to return to the clinical facility having refrained from eating and drinking for 2 hours. An assessment of air blast hypersensitivity and examinations of oral soft and hard tissue were performed at the baseline. Subjects were provided a professional in-office prophylaxis with their assigned prophylaxis paste. A post hypersensitivity examination was performed immediately after the oral prophylaxis. RESULTS: All subjects completed the study. At the post-hypersensitivity examination, subjects assigned to the Test Paste group and Control Paste group both exhibited statistically significant (P = 0000) reductions (compared to baseline), to air blast hypersensitivity of 44.7% and 25.6%, respectively. At the post-hypersensitivity examination, subjects in the Test Paste group exhibited a statistically significant (P = 0.005) reduction of 24.4% in mean air blast hypersensitivity scores as compared to the Control Paste group.

Measuring psychological flexibility in medical students and residents: a psychometric analysis.

PURPOSE: Psychological flexibility involves mindful awareness of our thoughts and feelings without allowing them to prohibit acting consistently with our values and may have important implications for patient-centered clinical care. Although psychological flexibility appears quite relevant to the training and development of health care providers, prior research has not evaluated measures of psychological flexibility in medical learners. Therefore, we investigated the validity of our learners' responses to three measures related to psychological flexibility. METHODS: Fourth-year medical students and residents (n=275) completed three measures of overlapping aspects of psychological flexibility: (1) Acceptance and Action Questionnaire-II (AAQ-II); (2) Cognitive Fusion Questionnaire (CFQ); and (3) Mindful Attention and Awareness Questionnaire (MAAS). We evaluated five aspects of construct validity: content, response process, internal structure, relationship with other variables, and consequences. RESULTS: We found good internal consistency for responses on the AAQ (α=0.93), MAAS (α=0.92), and CFQ (α=0.95). Factor analyses demonstrated a reasonable fit to previously published factor structures. As expected, scores on all three measures were moderately correlated with one another and with a measure of life satisfaction (p<0.01). CONCLUSION: Our findings provide preliminary evidence supporting validity of the psychological flexibility construct in a medical education sample. As psychological flexibility is a central concept underlying self-awareness, this work may have important implications for clinical training and practice.

Use of a biosimilar granulocyte colony-stimulating factor for peripheral blood stem cell mobilization: an analysis of mobilization and engraftment.

Peripheral blood haematopoietic progenitor cell mobilization has become a standard procedure prior to autologous stem cell transplantation. Biosimilar granulocyte colony-stimulating factors (GCSF) have recently been awarded European Union (EU) licences for stem cell mobilization but data for their use in this context remain limited. The biosimilar GCSF, Ratiograstim(®) (Ratiopharm, Ulm, Germany) was granted an EU licence in September 2008 and incorporated into clinical practice in the Wessex Blood and Marrow Transplantation Programme in December 2008. Data were retrospectively collected for 154 consecutive patients undergoing peripheral blood stem cell harvest between January 2009 and December 2011 using the biosimilar GCSF. 131 consecutive patients from the preceding 3 years, who had received Neupogen(®) , were used as a control. We analysed both parameters relevant to stem cell collection and engraftment data, where patients proceeded to transplantation. We found no statistically significant difference between the two groups when comparing CD34 predictors, total number of CD34(+) stem cells collected, number of days required for collection, or for time to engraftment. This is, to our knowledge, the largest direct comparison of a biosimilar GCSF with originator GCSF for stem cell mobilization. The use of biosimilar GCSF can produce a significant cost saving, allowing investment in other areas of stem cell transplantation.

Mumps virus encephalomyelitis in a 19-year old male patient with an undefined severe combined immunodeficiency post-haematopoietic bone marrow transplantation: a rare fatal complication.

We describe a rare case of fatal mumps encephalomyelitis occurring in 19-year old male following matched unrelated donor peripheral blood haematopoietic stem cell transplantation (HSCT). The indication for HSCT was for an undefined form of severe combined immunodeficiency (SCID). Molecular typing of the mumps viral RNA isolated from neural tissue indicated that the infection was acquired at the time of a mumps outbreak in England and Wales that occurred between 2004 and 2006. This case highlights the importance of considering mumps in the differential diagnosis of central nervous system infection in highly immunosuppressed patients.

Impact of disease-specific orientation on new graduate nurse satisfaction and knowledge retention.

Transition from student to novice nurse can be especially challenging, and a weak orientation can further complicate this difficult time for new graduate nurses. The neuroscience field is complex, and orientation can cause new nurses to lack a comprehensive understanding of their specialty, resulting in a task-focused approach to bedside care. Using a convenience sample and both qualitative and quantitative data, this study implements a disease-specific orientation track for new graduate nurses to spotlight the most common neurological diagnoses and disorders while concentrating on building an understanding of how to provide the best care possible to these patients. This article reports the outcomes achieved from the first phase of the study including improved clinical competence, readiness and retention of knowledge, overall satisfaction with orientation, and increased comfort level in caring for the neurological patient. In addition, the feedback and information gathered have provided a foundation for the project to be tailored and continued to further improve these results with future new graduate nurses on the neuroscience unit.

Love attitudes and relationship experience.

The present study examined the association of love attitudes with the initiation, maintenance, and dissolution of relationships. Respondents completed the Love Attitudes Scale and a questionnaire designed to measure experiences at each stage of relationship development. Ludus was relevant to all stages of relationship development; ludic attitudes were associated with absence of concern for partner loyalty, short and uncommitted relationships, and positive feelings about relationship dissolution. Pragma was associated primarily with relationship initiation (i.e., selection of an appropriate partner). Agape and Mania were most apparent during maintenance, as evidenced by relationships with indicators of involvement and loyalty. Agape, Mania, and Eros related to negative emotions at the point of relationship dissolution.