Teaching at the Bedside: Maximal impact in Minimal Time

Academic physicians encounter many demands on their time including patient care, quality and performance requirements, research, and education. In an era when patient volume is prioritized and competition for research funding is intense, there is a risk that medical education will become marginalized. Bedside teaching, a responsibility of academic physicians regardless of professional track, is challenged in particular out of concern that it generates inefficiency, and distractions from direct patient care, and can distort physician–patient relationships. At the same time, the bedside is a powerful location for teaching as learners more easily engage with educational content when they can directly see its practical relevance for patient care. Also, bedside teaching enables patients and family members to engage directly in the educational process. Successful bedside teaching can be aided by consideration of four factors: climate, attention, reasoning, and evaluation. Creating a safe environment for learning and patient care is essential. We recommend that educators set expectations about use of medical jargon and engagement of the patient and family before they enter the patient room with trainees. Keep learners focused by asking relevant questions of all members of the team and by maintaining a collective leadership style. Assess and model clinical reasoning through a hypothesis-driven approach that explores the rationale for clinical decisions. Focused, specific, real-time feedback is essential for the learner to modify behaviors for future patient encounters. Together, these strategies may alleviate challenges associated with bedside teaching and ensure it remains a part of physician practice in academic medicine

Longitudinal Milestone Assessment Extending Through Subspecialty Training: The Relationship Between ACGME Internal Medicine Residency Milestones and Subsequent Pulmonary and Critical Care Fellowship Milestones

Purpose Accreditation Council for Graduate Medical Education (ACGME) milestones were implemented across medical subspecialties in 2015. Although milestones were proposed as a longitudinal assessment tool potentially providing opportunities for early implementation of individualized fellowship learning plans, the association of subspecialty fellowship ratings with prior residency ratings remains unclear. This study aimed to assess the relationship between internal medicine (IM) residency milestones and pulmonary and critical care medicine (PCCM) fellowship milestones. Method A multicenter retrospective cohort analysis was conducted for all PCCM trainees in ACGME-accredited PCCM fellowship programs, 2017–2018, who had complete prior IM milestone ratings from 2014 to 2017. Only professionalism and interpersonal and communication skills (ICS) were included based on shared anchors between IM and PCCM milestones. Using a generalized estimating equations model, the association of PCCM milestones ≤ 2.5 during the first fellowship year with corresponding IM subcompetencies was assessed at each time point, nested by program. Statistical significance was determined using logistic regression. Results The study included 354 unique PCCM fellows. For ICS and professionalism subcompetencies, fellows with higher IM ratings were less likely to obtain PCCM ratings ≤ 2.5 during the first fellowship year. Each ICS subcompetency was significantly associated with future lapses in fellowship (ICS01: β = −0.67, P = .003; ICS02: β = −0.70, P = .001; ICS03: β = −0.60, P = .004) at various residency time points. Similar associations were noted for PROF03 (β = −0.57, P = .007). Conclusions Findings demonstrated an association between IM milestone ratings and low milestone ratings during PCCM fellowship. IM trainees with low ratings in several professionalism and ICS subcompetencies were more likely to be rated ≤ 2.5 during the first PCCM fellowship year. This highlights a potential use of longitudinal milestones to target educational gaps at the beginning of PCCM fellowship

Expectations and outcomes of prolonged mechanical ventilation*

Prolonged mechanical ventilation (PMV) provision is increasing markedly despite poor patient outcomes. Misunderstanding prognosis in the PMV decision making process could provide an explanation to this phenomenon. Therefore, we aimed to compare PMV decision makers' expectations for long-term patient outcomes with prospectively observed outcomes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Nonadhesive Culture System as a Model of Rapid Sphere Formation with Cancer Stem Cell Properties

BACKGROUND: Cancer stem cells (CSCs) play an important role in tumor initiation, progression, and metastasis and are responsible for high therapeutic failure rates. Identification and characterization of CSC are crucial for facilitating the monitoring, therapy, or prevention of cancer. Great efforts have been paid to develop a more effective methodology. Nevertheless, the ideal model for CSC research is still evolving. In this study, we created a nonadhesive culture system to enrich CSCs from human oral squamous cell carcinoma cell lines with sphere formation and to characterize their CSC properties further. METHODS: A nonadhesive culture system was designed to generate spheres from the SAS and OECM-1 cell lines. A subsequent investigation of their CSC properties, including stemness, self-renewal, and chemo- and radioresistance in vitro, as well as tumor initiation capacity in vivo, was also performed. RESULTS: Spheres were formed cost-effectively and time-efficiently within 5 to 7 days. Moreover, we proved that these spheres expressed putative stem cell markers and exhibited chemoradiotherapeutic resistance, in addition to tumor-initiating and self-renewal capabilities. CONCLUSIONS: Using this nonadhesive culture system, we successfully established a rapid and cost-effective model that exhibits the characteristics of CSCs and can be used in cancer research

Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Objectives: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods: In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results: Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. Conclusions: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. HIV Medicin

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome