Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency.

PURPOSE: Patients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hematopoietic stem cell transplant (HSCT) or gene therapy. Beginning in 1990, ERT was performed with PEGylated bovine intestinal ADA (ADAGEN®). In 2019, a PEGylated recombinant bovine ADA (Revcovi®) replaced ADAGEN following studies in older patients previously treated with ADAGEN for many years. There are limited longitudinal data on ERT-naïve newborns treated with Revcovi. METHODS: We report our clinical experience with Revcovi as initial bridge therapy in three newly diagnosed infants with ADA-SCID, along with comprehensive biochemical and immunologic data. RESULTS: Revcovi was initiated at twice weekly dosing (0.2 mg/kg intramuscularly), and monitored by following plasma ADA activity and the concentration of total deoxyadenosine nucleotides (dAXP) in erythrocytes. All patients rapidly achieved a biochemically effective level of plasma ADA activity, and red cell dAXP were eliminated within 2-3 months. Two patients reconstituted B-cells and NK-cells within the first month of ERT, followed by naive T-cells one month later. The third patient reconstituted all lymphocyte subsets within the first month of ERT. One patient experienced declining lymphocyte counts with improvement following Revcovi dose escalation. Two patients developed early, self-resolving thrombocytosis, but no thromboembolic events occurred. CONCLUSION: Revcovi was safe and effective as initial therapy to restore immune function in these newly diagnosed infants with ADA-SCID, however, time course and degree of reconstitution varied. Revcovi dose may need to be optimized based on immune reconstitution, clinical status, and biochemical data.

Case Report: Nontuberculous mycobacterial infections in children with complete DiGeorge anomaly.

Children with complete DiGeorge anomaly (cDGA) have congenital athymia, resulting in severe T cell immunodeficiency and susceptibility to a broad range of infections. We report the clinical course, immunologic phenotypes, treatment, and outcomes of three cases of disseminated nontuberculous mycobacterial infections (NTM) in patients with cDGA who underwent cultured thymus tissue implantation (CTTI). Two patients were diagnosed with Mycobacterium avium complex (MAC) and one patient with Mycobacterium kansasii. All three patients required protracted therapy with multiple antimycobacterial agents. One patient, who was treated with steroids due to concern for immune reconstitution inflammatory syndrome (IRIS), died due to MAC infection. Two patients have completed therapy and are alive and well. T cell counts and cultured thymus tissue biopsies demonstrated good thymic function and thymopoiesis despite NTM infection. Based on our experience with these three patients, we recommend that providers strongly consider macrolide prophylaxis upon diagnosis of cDGA. We obtain mycobacterial blood cultures when cDGA patients have fevers without a localizing source. In cDGA patients with disseminated NTM, treatment should consist of at least two antimycobacterial medications and be provided in close consultation with an infectious diseases subspecialist. Therapy should be continued until T cell reconstitution is achieved.

Pilot evaluation of the stop, breathe & think mindfulness app for student clients on a college counseling center waitlist.

Objectives: College counseling centers face significant challenges meeting the mental health needs of their students and waitlists are common. Mobile apps offer a promising solution to increase access to resources while students wait for services. Methods: This pilot randomized controlled trial evaluated the feasibility and acceptability of a publicly available mindfulness app. Students on a counseling center waitlist (n = 23) were randomized to use the app or not, with assessments completed over four weeks. Results: Recruitment over three semesters was slow, leading to an underpowered trial. Participants reported high satisfaction and moderate app usage. Very preliminary support was found for potential app efficacy relative to the control condition, particularly for depression, anxiety, and overall distress. Weaker, mixed effects were found for mindfulness and values processes. Conclusions: Overall, these results provide mixed findings suggesting the potential benefits, but also challenges in using a mindfulness app for students waiting to receive counseling services.

Enhanced development of CD4+ gammadelta T cells in the absence of Itk results in elevated IgE production.

The Tec kinase Itk is critical for the development of alphabeta T cells as well as differentiation of CD4(+) T cells into Th2 cells. Itk null mice have defects in the production of Th2 cytokines; however, they paradoxically have significant elevations in serum IgE. Here we show that Itk null mice have increased numbers of gammadelta T cells in the thymus and spleen. This includes elevated numbers of CD4(+) gammadelta T cell, the majority of which carry the Vgamma1.1 and Vdelta6.2/3 gammadelta T-cell receptor with a distinct phenotype. The development of these CD4(+) gammadelta T cells is T cell intrinsic, independent of either major histocompatibility complex class I or class II, and is favored during development in the absence of Itk. Itk null CD4(+) gammadelta T cells secrete significant amounts of Th2 cytokines and can induce the secretion of IgE by wild-type B cells. Our data indicate that Itk plays important role in regulating gammadelta T-cell development and function. In addition, our data indicate that the elevated IgE observed in Itk-deficient mice is due in part to the enhanced development of CD4(+) gammadelta T cells in the absence of Itk.

A randomized controlled trial of behavior change counseling education for medical students.

BACKGROUND: Educating medical students about how to effectively counsel patients with negative health behaviors (i.e., lack of exercise, smoking) is vitally important. Behavior change counseling is a promising method that can be used by physicians to encourage positive changes in health behaviors. PURPOSE: To examine the effectiveness of a 2 h workshop in behavior change counseling for medical students. METHODS: This study used a pre-post control group design with 35 second-year medical students who were randomly assigned to participate in a behavior change counseling intervention or wait-list control group. Student knowledge and attitudes were assessed using multiple choice items and open-ended question prompts. Student skills were assessed via performance in a standardized patient encounter rated using the Behavior Change Counseling Index (BECCI). RESULTS: Student attitudes toward behavior change counseling were positive at both pre- and post-test assessment in both groups. Knowledge scores and BECCI total scores showed significantly greater improvement in the intervention group compared to the wait-list control group. CONCLUSIONS: This study found that a brief educational intervention had a positive impact on medical students' knowledge and skills in behavior change counseling, and that student attitudes about the counseling method were very positive.

A randomized dismantling trial of the open and engaged components of acceptance and commitment therapy in an online intervention for distressed college students.

This dismantling trial compared the effects of a full online Acceptance and Commitment Therapy (ACT) intervention to the isolated effects of the Open (i.e., acceptance, cognitive defusion) and Engaged (i.e., values, committed action) components of ACT. A sample of 181 distressed college students were randomized to one of four conditions: a 12-session full ACT website (Full), a version targeting the Open components (Open), a version targeting the Engaged components (Engaged), or waitlist. Participants in active conditions were also randomized to receive phone coaching or just email prompts to increase program adherence. All three ACT conditions significantly improved over time relative to the waitlist condition on the primary outcome of mental health symptoms. The Engaged and Full conditions had greater rates of reliable change on the primary outcome relative to waitlist, but not the Open condition. Similarly, only Engaged and Full conditions improved on positive mental health relative to waitlist. The Full condition had greater improvements on a few ACT process measures relative to Engaged and Open conditions, particularly cognitive fusion. Overall, results indicate targeting only the Open components of ACT was somewhat less effective, and that including both the Open and Engaged components led to greater decreases in cognitive fusion.

Patient perceptions of professionalism: implications for residency education.

OBJECTIVES The purpose of this study was three-fold: to identify which behavioural, communicative and personal presentation characteristics most closely represent patients' views of professionalism; to determine whether patients perceive resident doctors as displaying these characteristics, and to explore whether or not resident doctor professional behaviour creates an impression of clinical competence to the degree where patients perceive a decreased need for Attending Physician involvement. METHODS We carried out a descriptive, cross-sectional study at an academic centre. An anonymous, voluntary four-question survey with multiple items was administered to all adult patients or the parents of paediatric patients attending an ophthalmology clinic who were seen by a resident doctor followed by an Attending Physician. RESULTS A total of 133 of 148 (90%) surveys were returned. All the itemised characteristics of professionalism were reported to be important or very important to the majority of participants.The most important were: 'Pays attention to my concerns' (90%); 'Is compassionate' (83%), and 'Speaks in terms that I can understand' (83%). Although 85% of respondents reported that resident doctors demonstrated all the characteristics of professionalism listed on the survey, 83% of participants stated that it was important or very important that residents have Attending Physician involvement. CONCLUSIONS Patient-centred components of professionalism, such as communication skills and compassion, are more important to patients than social behaviours, such as appearance and acknowledgement of family members. Resident doctors are perceived to display a high level of professionalism during patient care. Patients clearly desire direct resident doctor

Developing an educator network: the effect of a teaching scholars program in the health professions on networking and productivity.

BACKGROUND: Teaching Scholars Programs are designed to enhance productivity and faculty retention. The formation of an increased network may be a facilitative mechanism. PURPOSES: This study determined if participants increased their educational network and if the increase affected productivity. METHODS: Researchers interviewed Teaching Scholars participants for pre- and postparticipation members of their educational network and issues related to network formation and conducted a structured vita analysis. Researchers used social network analysis (SNA) to describe the networks and regression to determine the relationship between network and productivity. RESULTS: Educational networks increased with participation (p <.001) but showed little or no effect on productivity. SNA revealed a decrease of participants with no network, increase in connections among participants, and increase in connections to central services personnel. Researchers identified six themes from the participants' comments. CONCLUSIONS: This relatively modest program demonstrated a small effect on productivity through the increased network.

Implementation of Health Insurance Support Tools in Community Health Centers.

BACKGROUND: Health information technology (HIT) provides new opportunities for primary care clinics to support patients with health insurance enrollment and maintenance. We present strategies, early findings, and clinic reflections on the development and implementation of HIT tools designed to streamline and improve health insurance tracking at community health centers. METHODS: We are conducting a hybrid implementation-effectiveness trial to assess novel health insurance enrollment and support tools in primary care clinics. Twenty-three clinics in 7 health centers from the OCHIN practice-based research network are participating in the implementation component of the trial. Participating health centers were randomized to 1 of 2 levels of implementation support, including arm 1 (n = 4 health centers, 11 clinic sites) that received HIT tools and educational materials and arm 2 (n = 3 health centers, 12 clinic sites) that received HIT tools, educational materials, and individualized implementation support with a practice coach. We used mixed-methods (qualitative and quantitative) to assess tool use rates and facilitators and barriers to implementation in the first 6 months. RESULTS: Clinics reported favorable attitudes toward the HIT tools, which replace less efficient and more cumbersome processes, and reflect on the importance of clinic engagement in tool development and refinement. Five of 7 health centers are now regularly using the tools and are actively working to increase tool use. Six months after formal implementation, arm 2 clinics demonstrated higher rates of tool use, compared with arm 1. DISCUSSION: These results highlight the value of early clinic input in tool development, the potential benefit of practice coaching during HIT tool development and implementation, and a novel method for coupling a hybrid implementation-effectiveness design with principles of improvement science in primary care research.

Optimal learning environments from the perspective of resident physicians and associations with accreditation length.

BACKGROUND: Indicators of program quality in graduate medical education have not been thoroughly well developed or studied. This study explores resident physicians' perceptions of program quality and associations with an external quality indicator. METHOD: Responses to two open-ended questions about program strengths and areas in need of improvement were analyzed for 392 residents from 14 specialty programs that were reaccredited between 1999 and 2005. Computerized text analysis facilitated reliable categorization of 1,502 comments. Mann-Whitney U tests and nonparametric analyses for correlated data were used to examine associations between resident perceptions and accreditation length. RESULTS: The most frequently mentioned program strengths were related to the quality of faculty, exposure to patients, education, and the social environment. Of these core strengths, residents in programs with longer cycle lengths had significantly more comments about the quality of faculty in their program. CONCLUSIONS: Resident feedback can provide beneficial information about dimensions of program quality and the learning environment.

Public accountants' field dependence: Canadian evidence.

The cognitive styles of 113 practicing, professional accountants from Nova Scotia, Canada were examined using the Group Embedded Figures Test. They completed a demographic survey for descriptive information as well as their rank in the firm and preferred area of professional practice. Analysis suggested professional accountants tend to be more analytical than intuitive in cognitive style and, consistent with recent findings in other fields, men and women in accounting do not appear to be different in cognitive style. No statistically significant differences were found on the embedded figures scores across ranks of trainee, manager, and partner or across select, preferred areas of professional practice.

Course of Chronic Trypanosoma cruzi Infection after Treatment Based on Parasitological and Serological Tests: A Systematic Review of Follow-Up Studies.

BACKGROUND: Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). It is endemic in Latin American countries outside the Caribbean. The current criterion for cure in the chronic phase of the disease is the negativization of at least two serological tests such as enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) and indirect hemagglutination assay (IHA). The serological evolution of treated subjects with chronic T. cruzi infection is variable. Treatment failure is indicated by a positive parasitological and/or molecular test (persistence of parasitemia). OBJECTIVES: To summarize the pattern of response to treatment of parasitological, molecular and serological tests performed during the follow-up of subjects with chronic T. cruzi infection. METHODS: Electronic searches in relevant databases and screening of citations of potentially eligible articles were accomplished. Organizations focusing on neglected infectious diseases were asked for help in identifying relevant studies. Included studies were randomized controlled trials (RCTs), quasi-RCTs, and cohort studies involving adults and children with chronic infection who received trypanocidal treatment (benznidazole or nifurtimox) and were followed over time. The assessment of risk of bias was performed separately for each study design. The Cochrane Collaboration's tool and the guidelines developed by Hayden et al. were used. Two reviewers extracted all data independently. A third review author was consulted in case of discordant opinion. Additional analyses were defined in ad-hoc basis. Scatter plots for percentage of positive parasitological and molecular tests and for negative serological tests were developed by using the lowess curve technique. Heterogeneity was measured by I2. The protocol was registered in PROSPERO, an international prospective register of systematic review protocols (Registration Number CRD42012002162). RESULTS: Out of 2,136 citations screened, 54 studies (six RCTs and 48 cohort studies) were included. The smoothed curves for positive xenodiagnosis and positive polymerase chain reaction (PCR) were characterized by a sharp decrease at twelve month posttreatment. Afterwards, they reached 10-20% and 40% for xenodiagnosis and PCR, respectively. The smoothed curves for negative conventional serological tests increased up to 10% after 48 months of treatment. In the long-term, the rate of negativization was between 20% and 45%. The main sources of bias identified across cohort studies were the lack of control for confounding and attrition bias. In general, RCTs were judged as low risk of bias in all domains. The level of heterogeneity across included studies was moderate to high. Additional analysis were incomplete because of the limited availability of data. In this regard, the country of origin of study participants might affect the results of parasitological and molecular tests, while the level of risk of bias might affect serological outcomes. Subgroup analysis suggested that seronegativization occurs earlier in children compared to adults. CONCLUSIONS: We acknowledge that there is a dynamic pattern of response based on parasitological, molecular and serological tests in subjects chronically infected with T. cruzi after treatment. Our findings suggest a trypanocidal effect in the long-term follow-up. Further research is needed to explore potential sources of heterogeneity and to conduct reliable subgroup analysis.

Identifying areas for curricular program improvement based on perceptions of skills, competencies, and performance.

OBJECTIVE: Educational program evaluation and program improvement are processes that can be enhanced by involving multiple stakeholders and measurement tools. The purpose of this study was to compare faculty and resident physician perceptions of both teaching quality and resident competence for 13 core psychiatric skills and the six Accreditation Council for Graduate Medical Education general competencies. Additionally, resident performance as assessed by portfolios was descriptively examined relative to these perceptions of skills and competencies. Using this combination of data, the authors propose a useful approach for identifying areas for improvement within a medical residency's program curriculum. METHODS: Ten teaching faculty members (100%) and 18 residents (82%) within a psychiatry department completed parallel surveys. Trained raters scored resident-completed portfolio entries. Nonparametric and descriptive analyses were used to compare the various data sources. RESULTS: In general, faculty and residents showed congruence in their perceptions about resident performance. They agreed on the quality of teaching skills and general competencies. General competency scores from the portfolios were congruent with this perspective. However, there were mismatches in perceptions and performance on portfolios for some areas. Of the 13 core psychiatric skills examined, only one area, neuropsychiatry, was rated below average by both faculty and residents, while the median portfolio performance score was below competent for four skills, including neuropsychiatry. Faculty rated resident competence significantly higher than residents rated themselves for biopsychosocial formulation and medical psychiatry. CONCLUSION: This study describes and highlights the usefulness of a multidimensional approach that includes resident and faculty perspectives and externally rated performance measures to assist in identifying potential target areas for curriculum improvement.

Educational development program for residency program directors and coordinators.

BACKGROUND: Residency program directors and program coordinators have increasing demands placed on them by accrediting agencies and require educational development specifically tailored to their needs. DESCRIPTION: We created, piloted, and evaluated an educational development program consisting of 10 sessions spanning 1 year for program directors and a parallel set of sessions for program coordinators. EVALUATION: On average, more than half the residency programs participated in the sessions. Programs improved in residency activities related to their program's handbook, interviewing, evaluations, rotation descriptions, and program evaluation. They did not improve in educational scholarly activities. Program directors and coordinators indicated that the program improved their skills, and they would recommend the program for others. CONCLUSIONS: This 10-session program improved important elements of residency education and was favorably received.

A Graduate Medical Education Initiative to Promote Professional Excellence Among Residency Program Coordinators.

BACKGROUND: The authors describe the scope and impact of a professional development program for residency and fellowship program coordinators (PCs) at the University of Arkansas for Medical Sciences (UAMS) College of Medicine. PCs are vital in the success of their residency programs, yet few articles to date have addressed their increasingly complex roles. PURPOSE: This exploratory study examines PCs' professional characteristics, perceptions that influence professional development meeting attendance, and the impact of the Program Coordinators' Organization (PCO). METHODS: All 44 PCs serving 53 residency and fellowship programs at UAMS were surveyed about their perceptions of the PCO in January 2006. RESULTS: The majority of respondents agreed that the PCO has improved their abilities and interactions with their supervisors, colleagues, and residents and that the PCO has made an institution-wide impact on residency education. CONCLUSIONS: Sponsoring a PCO may be an effective tool for organizations to enhance the role of PCs and their graduate medical education programs.