Clinical and experimental treatment of allergic asthma with an emphasis on allergen immunotherapy and its mechanisms.

Allergen immunotherapy (AIT) is currently the only form of treatment that modifies allergic asthma. Pharmacotherapy alone seeks to control the symptoms of allergic asthma, allergic rhinitis, and other atopic conditions. In contrast, AIT can induce long-term physiological modifications through the immune system. AIT enables individuals to live improved lives many years after treatment ends, where they are desensitized to the allergen(s) used or no longer have significant allergic reactions upon allergen provocation. The leading forms of treatment with AIT involve injections of allergen extracts with increasing doses via the subcutaneous route or drops/tablets via the sublingual route for several years. Since the initial attempts at this treatment as early as 1911 by Leonard Noon, the mechanisms by which AIT operates remain unclear. This literature-based review provides the primary care practitioner with a current understanding of the mechanisms of AIT, including its treatment safety, protocols, and long-term efficacy. The primary mechanisms underlying AIT include changes in immunoglobulin classes (IgA, IgE, and IgG), immunosuppressive regulatory T-cell induction, helper T cell type 2 to helper T cell type 1 cell/cytokine profile shifts, decreased early-phase reaction activity and mediators, and increased production of IL-10, IL-35, TGF-ß, and IFN-γ. Using the databases PubMed and Embase, a selective literature search was conducted searching for English, full-text, reviews published between 2015 and 2022 using the keywords (with wildcards) "allerg*," "immunotherap*," "mechanis*," and "asthma." Among the cited references, additional references were identified using a manual search.

Medical students' perception of behaviors in the clinical learning environment evolve with increasing clinical exposure as measured with situational video vignettes.

This cross-sectional study involved matriculating, mid-level and graduating medical students (n = 723) who participated in specific transition courses in our medical school curriculum between August 2016 and March 2019. We used a mixed-methods approach (survey and analysis of narrative comments) to study the evolution in perception of the learning environment by medical students with increasing clinical exposure using four different video vignettes. Differences in student perceptions of mistreatment exists at various levels of training. Compared to graduating students, matriculating students were more likely to perceive reprimanding a student on being late as appropriate behavior (80.5% vs 53.3%, p = 0.001), whereas a significantly higher proportion of the graduating students (15.3%, p = 0.001) perceived it as mistreatment. A majority of the matriculating students (84%, p = 0.001) considered the case of an eager student as mistreatment, while a significantly higher proportion of the graduating students (59.5%, p = 0.001) did not think it was mistreatment. Qualitative analysis of comments from students at different stages of training displayed an increased appreciation of their professional responsibilities and nuanced appreciation of body language and tone as contributing factors in determining whether a situation represented inappropriate behavior. Our results demonstrate that students' perceptions of inappropriate behaviors evolve with increased clinical exposure.

A model of influences on the clinical learning environment: the case for change at one U.S. medical school.

BACKGROUND: The learning environment within a school of medicine influences medical students' values and their professional development. Despite national requirements to monitor the learning environment, mistreatment of medical students persists. METHODS: We designed a program called WE SMILE: We can Eradicate Student Mistreatment In the Learning Environment with a vision to enhance trainee and faculty awareness and ultimately eliminate medical student mistreatment. We provide a description of our program and early outcomes. RESULTS: The program has enhanced student awareness of what constitutes mistreatment and how to report it. Faculty members are also aware of the formal processes and procedures for review of such incidents. Our proposed model of influences on the learning environment and the clinical workforce informs the quality of trainee education and safety of patient care. Institutional leadership and culture play a prominent role in this model. Our integrated institutional response to learning environment concerns is offered as a strategy to improve policy awareness, reporting and management of student mistreatment concerns. CONCLUSIONS: Our WE SMILE program was developed to enhance education and awareness of what constitutes mistreatment and to provide multiple pathways for student reporting, with clear responsibilities for review, adjudication and enforcement. The program is demonstrating several signs of early success and is offered as a strategy for other schools to adopt or adapt. We have recognized a delicate balance between preserving student anonymity and informing them of specific actions taken. Providing students and other stakeholders with clear evidence of institutional response and accountability remains a key challenge. Multiple methods of reporting have been advantageous in eliciting information on learning environment infringements. These routes and types of reporting have enhanced our understanding of student perceptions and the specific contexts in which mistreatment occurs, allowing for targeted interventions. A common platform across the healthcare professions to report and review concerns has afforded us opportunities to deal with interprofessional issues in a respectful and trustworthy manner. We offer a model of learning environment influences with leadership and institutional culture at the helm, as a way to frame a comprehensive perspective on this challenging and complex concern.

Case Studies for Recognizing Appropriate and Inappropriate Behaviors in the Clinical Learning Environment.

Introduction: The Association of American Medical Colleges surveys graduating medical students regarding the persistent prevalence of learning environment concerns. This training module is designed to increase awareness of appropriate and inappropriate behaviors in the clinical learning environment among medical professionals and trainees. Methods: An introductory PowerPoint presents the types of inappropriate behaviors that may be observed in the clinical learning environment along with institution-specific mechanisms for reporting such behaviors. We have also created six vignettes depicting various scenarios that trainees may encounter. The vignettes are presented in both text and video format and may be used in any combination. The entire module consisting of the PowerPoint presentation and the case studies can be delivered in 90 minutes to a large group of learners. Learners are divided into smaller groups of six to eight for discussions. The presentation and discussion can be done by a single or multiple facilitators. The target audience is primarily medical professionals and trainees at various levels of clinical exposure. Results: Since implementation of this training module at our institution, awareness of what constitutes mistreatment and how to report it has increased to nearly 100%. Representative institutional responses are provided for each vignette. Discussion: This training module can be presented to medical students, residents, and faculty at different stages of their professional development. We have enhanced learner awareness of what constitutes mistreatment and how to report these events. We offer these educational materials for other institutions to adapt and use in their specific institutional contexts.

Academic medicine change management: the power of the liaison committee on medical education accreditation process.

Stony Brook University School of Medicine (SBU SOM) used a Liaison Committee on Medical Education (LCME) site visit to design a change management approach that engaged students, revitalized faculty, and enabled significant, positive institutional transformation while flexibly responding to concurrent leadership transitions. This "from-the-trenches" description of novel LCME site-visit-related processes may provide an educational program quality improvement template for other U.S. medical schools. The SBU SOM site visit processes were proactively organized within five phases: (1) planning (4 months), (2) data gathering (12 months), (3) documentation (6 months), (4) visit readiness (2 months), and (5) visit follow-up (16 months). The authors explain the key activities associated with each phase.The SBU SOM internal leadership team designed new LCME-driven educational performance reports to identify challenging aspects of the educational program (e.g., timeliness of grades submitted, midcourse feedback completeness, clerkship grading variability across affiliate sites, learning environment or student mistreatment incidents). This LCME process increased institutional awareness, identified the school's LCME vulnerabilities, organized corrective actions, engaged key stakeholders in communication, ensured leadership buy-in, and monitored successes. The authors' strategies for success included establishing a strong internal LCME leadership team, proactively setting deadlines for all phases of the LCME process, assessing and communicating vulnerabilities and action plans, building multidisciplinary working groups, leveraging information technology, educating key stakeholders through meetings, retreats, and consultants, and conducting a mock site visit. The urgency associated with an impending high-stakes LCME site visit can facilitate positive, local, educational program quality improvement.

Dexamethasone therapy interferes with the development of the neutrophil oxidative burst in vitro in very low birthweight infants.

Dexamethasone therapy is used in the treatment of chronic lung disease in very low birthweight (VLBW) neonates. However, several significant side effects have been observed in these patients, including an increased incidence of infection. We initiated a pilot study to examine the in vitro function of neutrophils from dexamethasone-treated VLBW infants. Following a 1-week course of dexamethasone, VLBW infants failed to demonstrate the increased oxidative burst that was observed in the age- and weight-matched untreated infants. These observations support recent evidence raising concern about effects on other organs when using dexamethasone in mechanically ventilated infants. In this example, impaired oxidative burst may be among the cellular factors contributing to the increased risk of infection during corticosteroid use in VLBW neonates in the neonatal intensive care setting.

In vivo effect of recombinant human granulocyte colony-stimulating factor on phagocytic function and oxidative burst activity in septic neutropenic neonates.

Neutrophil dysfunction may contribute to an increased risk of sepsis in very-low-birth-weight (VLBW) neonates. The current study was designed to determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects absolute neutrophil count (ANC), phagocytic function, and oxidative burst in neutropenic VLBW neonates. Fourteen ventilated VLBW neonates were treated with rhG-CSF (10 microg/kg/day x 3 days i.v.). Phagocytic activity and oxidative burst were assessed before and after treatment with rhG-CSF using flow cytometry and fluorescence labeled opsonized Staphylococcus aureus. Control (nonseptic, nonneutropenic, n = 4), preeclamptic neutropenic (PET; nonseptic, n = 5), and septic neutropenic (n = 5) neonates with a gestational age ranging from 24 to 30 weeks were studied. In both PET and septic neonates, posttreatment phagocytosis more than doubled, but did not achieve matching control levels, whereas rhG-CSF treatment maintained the level of the phagocytic activity in the control group. The oxidative burst increased in all groups, but, again, PET and septic groups did not achieve matching control values. These effects occurred independent of a 2- to 12-fold increase in ANC. These results suggest that other disease-specific factors delay full functional recovery even after rhG-CSF treatment. We speculate that PET and septic neonates may remain susceptible to infection due to deficient neutrophil-killing capacity, even though their ANC returns to normal ranges. Augmenting immune function beyond the immediate period of ANC recovery suggests that prophylaxis with rhG-CSF may be an important risk reduction strategy for susceptible VLBW neonates.

Intravenous (IV) anti-D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti-D by FcgammaRIIa and FcgammaRIIIa polymorphisms.

Intravenous (IV) anti-D and IV immunoglobulin (IVIG) slow the Fcgamma receptor (FcgammaR)-mediated destruction of antibody-coated platelets in patients with immune thrombocytopenic purpura (ITP). This pilot study explored the mechanism of these immunoglobulin preparations by measuring interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), IL-6 and tumour necrosis factor alpha (TNFalpha), before and after infusion and by assessing the effect of FcgammaRIIa and FcgammaRIIIa polymorphisms on both cytokine and haematologic responses to anti-D. Following IVIG, only IL-10 was increased at 2 h and MCP-1 on day 7 (P < 0.05). In contrast, 2 h after anti-D infusion, plasma levels of all four cytokines were increased (P < 0.01); five of six patients with the highest MCP-1, IL-6 and TNFalpha levels had chills. Higher IL-10 levels correlated with platelet increases at 24 h and haemoglobin decreases at day 7 (P < 0.025). Patients with the FcgammaRIIa-131HH genotype had significantly higher MCP-1, IL-6 and TNFalpha levels. Patients with the FcgammaRIIIa-158VF genotype had higher platelet increments at day 7 (P < 0.05). Soluble CD16 (sCD16) was increased 2 h after IV anti-D; day 7 levels correlated with day 7 haemoglobin decreases (P < 0.01). In conclusion, the relationship of FcgammaRIIa and FcgammaRIIIa polymorphisms with both cytokine levels and platelet increments implicated these receptors in responses to anti-D and supported different mechanisms of FcgammaR interaction to those seen with IVIG.