Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dose viral therapies in humans, including immune responses and adverse effects such as genotoxicity, hepatotoxicity, thrombotic microangiopathy, and neurotoxicity. In this review, we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing technologies. We discuss how rAAVs are being employed in ongoing clinical trials for ocular, neurological, metabolic, hematological, neuromuscular, and cardiovascular diseases as well as cancers. We outline immune responses triggered by rAAV, address associated side effects, and discuss strategies to mitigate these reactions. We hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

Diagnosis and Management of Riga-Fede Disease: A Case Series.

In this case series, we present four unique cases of Riga-Fede disease (RFD), a rare disorder characterized by mucosal trauma as a result of repetitive tongue protrusion against the incisors, leading to the development of a large oral mass/ulceration. Due to the rapid development and growth of these lesions mimicking malignancy, it is important for the general and pediatric otolaryngologist to correctly diagnose and treat this benign disorder. This series highlights the variable clinical presentations, along with comorbidities of RFD, as well as the importance of interdisciplinary care between the pediatric otolaryngologist and pediatric dentist in its management. Laryngoscope, 2024.

Crowdsourced Feedback to Improve Resident Physician Error Disclosure Skills: A Randomized Clinical Trial.

Importance: Residents must prepare for effective communication with patients after medical errors. The video-based communication assessment (VCA) is software that plays video of a patient scenario, asks the physician to record what they would say, engages crowdsourced laypeople to rate audio recordings of physician responses, and presents feedback to physicians. Objective: To evaluate the effectiveness of VCA feedback in resident error disclosure skill training. Design, Setting, and Participants: This single-blinded, randomized clinical trial was conducted from July 2022 to May 2023 at 7 US internal medicine and family medicine residencies (10 total sites). Participants were second-year residents attending required teaching conferences. Data analysis was performed from July to December 2023. Intervention: Residents completed 2 VCA cases at time 1 and were randomized to the intervention, an individual feedback report provided in the VCA application after 2 weeks, or to control, in which feedback was not provided until after time 2. Residents completed 2 additional VCA cases after 4 weeks (time 2). Main Outcomes and Measures: Panels of crowdsourced laypeople rated recordings of residents disclosing simulated medical errors to create scores on a 5-point scale. Reports included learning points derived from layperson comments. Mean time 2 ratings were compared to test the hypothesis that residents who had access to feedback on their time 1 performance would score higher at time 2 than those without feedback access. Residents were surveyed about demographic characteristics, disclosure experience, and feedback use. The intervention's effect was examined using analysis of covariance. Results: A total of 146 residents (87 [60.0%] aged 25-29 years; 60 female [41.0%]) completed the time 1 VCA, and 103 (70.5%) completed the time 2 VCA (53 randomized to intervention and 50 randomized to control); of those, 28 (54.9%) reported reviewing their feedback. Analysis of covariance found a significant main effect of feedback between intervention and control groups at time 2 (mean [SD] score, 3.26 [0.45] vs 3.14 [0.39]; difference, 0.12; 95% CI, 0.08-0.48; P = .01). In post hoc comparisons restricted to residents without prior disclosure experience, intervention residents scored higher than those in the control group at time 2 (mean [SD] score, 3.33 [0.43] vs 3.09 [0.44]; difference, 0.24; 95% CI, 0.01-0.48; P = .007). Worse performance at time 1 was associated with increased likelihood of dropping out before time 2 (odds ratio, 2.89; 95% CI, 1.06-7.84; P = .04). Conclusions and Relevance: In this randomized clinical trial, self-directed review of crowdsourced feedback was associated with higher ratings of internal medicine and family medicine residents' error disclosure skill, particularly for those without real-life error disclosure experience, suggesting that such feedback may be an effective way for residency programs to address their requirement to prepare trainees for communicating with patients after medical harm. Trial Registration: ClinicalTrials.gov Identifier: NCT06234085.

Medical error: concept, characterization and management / Erro médico: conceito, caracterização e gestão

Abstract The objective of this study is to better understand the tensions involved in the fear of making an error due to the harm and risk this would pose to those involved. This is a qualitative study based on the narratives of the experiences lived by ten acting physicians in the state of São Paulo, Brazil. The concept and characterization of errors were discussed, as well as the fear of making an error, the near misses or error in itself, how to deal with errors and what to do to avoid them. The analysis indicates an excessive pressure in the medical profession for error-free practices, with a well-established physician-patient relationship to facilitate the management of medical errors. The error occurs but the lack of information and discussion often leads to its concealment due to fear of possible judgment by society or peers. The establishment of programs that encourage appropriate medical conduct in the event of an error requires coherent answers for humanization in Brazilian medical science.

Resumo O objetivo deste estudo é compreender as tensões presentes no medo de errar por conta dos riscos e danos que tal erro causaria aos envolvidos. Este é um estudo qualitativo baseado nas narrativas das experiências de 10 médicos atuantes no estado de São Paulo, Brasil. O conceito e a caracterização do erro foram discutidos, bem como o medo de cometê-lo, a proximidade com o erro, como lidar com ele e como evitá-lo. A análise aponta pressões excessivas no tocante a práticas sem erros na profissão médica, considerando a existência de uma relação médico-paciente bem estabelecida de forma a facilitar a gestão de erros médicos. Erros médicos ocorrem, mas a falta de informação e discussão sobre o tema costuma levar ao seu encobrimento, uma vez que médicos temem o possível julgamento feito pela sociedade e por seus pares. O estabelecimento de programas que encorajem a conduta médica apropriada caso um erro ocorra requer respostas coerentes para a humanização da ciência médica no Brasil.