Perceived Versus Actual Time of Prehospital Intubation by Paramedics.

Introduction: Situational awareness is essential during emergent procedures such as endotracheal intubation. Previous studies suggest that time distortion can occur during intubation. However, only in-hospital intubations performed by physicians have been studied. We aimed to determine whether time distortion affected paramedics performing intubation by examining the perceived vs actual total laryngoscopy time, defined as time elapsed from the laryngoscope blade entering the mouth until the endotracheal tube balloon passes the vocal cords. Methods: For this retrospective study we collected prehospital intubation data from a suburban, fire department-based emergency medical services (EMS) system from January 5, 2021-May 21, 2022. The perceived total laryngoscopy time was queried as a part of the electronic health record. Video laryngoscopy recordings were reviewed by a panel of experts to determine the actual time. Patients >18 years old who underwent intubation by paramedics with video laryngoscopy were included for analysis. The primary outcome was the difference between actual and perceived total laryngoscopy time. Secondary analysis examined the relationship between high time distortion, defined as the highest quartile of the primary outcome, and patient age, paramedic years of experience, perceived presence of difficult anatomy, excess secretions, use of rapid sequence intubation, and multiple intubation attempts. We conducted descriptive analysis followed by logistic regression analysis, chi-square tests, and Fisher exact tests when appropriate. Results: A total of 122 intubations were collected for analysis, and 10 were excluded due to lack of video recording. Final analysis included 112 intubations. Mean actual laryngoscopy time was 50.0 seconds (s) (95% confidence interval [CI] 43.7-56.3). Mean perceived laryngoscopy time was 27.8 s (95% CI 24.7-31.0). The median difference between actual and perceived time was 18 s (interquartile range 6-30). We calculated high time distortion as having a difference greater than 30 s between actual and perceived laryngoscopy time. None of the secondary variables had statistically significant associations with high time distortion. Overall, we show that the paramedic's perception of total laryngoscopy time is significantly underestimated even when accounting for paramedic experience and perceived airway difficulty. Conclusion: This study suggests that time distortion may lead to an unrecognized prolonged procedure time. Limitations include use of a convenience sample, small sample size, and potential uncollected confounding variables.

Large-scale phenotypic drug screen identifies neuroprotectants in zebrafish and mouse models of retinitis pigmentosa.

Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in multiple zebrafish and mouse RP models, reasoning drugs effective across species and/or independent of disease mutation may translate better clinically. We first performed a large-scale phenotypic drug screen for compounds promoting rod cell survival in a larval zebrafish model of inducible RP. We tested 2934 compounds, mostly human-approved drugs, across six concentrations, resulting in 113 compounds being identified as hits. Secondary tests of 42 high-priority hits confirmed eleven lead candidates. Leads were then evaluated in a series of mouse RP models in an effort to identify compounds effective across species and RP models, that is, potential pan-disease therapeutics. Nine of 11 leads exhibited neuroprotective effects in mouse primary photoreceptor cultures, and three promoted photoreceptor survival in mouse rd1 retinal explants. Both shared and complementary mechanisms of action were implicated across leads. Shared target tests implicated parp1-dependent cell death in our zebrafish RP model. Complementation tests revealed enhanced and additive/synergistic neuroprotective effects of paired drug combinations in mouse photoreceptor cultures and zebrafish, respectively. These results highlight the value of cross-species/multi-model phenotypic drug discovery and suggest combinatorial drug therapies may provide enhanced therapeutic benefits for RP patients.

Photoreceptors are the cells responsible for vision. They are part of the retina: the light-sensing tissue at the back of the eye. They come in two types: rods and cones. Rods specialise in night vision, while cones specialise in daytime colour vision. The death of these cells can cause a disease, called retinitis pigmentosa, that leads to vision loss. Symptoms often start in childhood with a gradual loss of night vision. Later on, loss of cone photoreceptors can lead to total blindness. Unfortunately, there are no treatments available that protect photoreceptor cells from dying. Research has identified drugs that can protect photoreceptors in animal models, but these drugs have failed in humans. The classic way to look for new treatments is to find drugs that target molecules implicated in a disease, and then test them to see if they are effective. Unfortunately, many drugs identified in this way fail in later stages of testing, either because they are ineffective, or because they have unacceptable side effects. One way to reverse this trend is to first test whether a drug is effective at curing a disease in animals, and later determining what it does at a molecular level. This could reveal whether drugs can protect photoreceptors before research to discover their molecular targets begins. Tests like this across different species could maximise the chances of finding a drug that works in humans, because if a drug works in several species, it is more likely to have shared target molecules across species. Applying this reasoning, Zhang et al. tested around 3,000 drug candidates for treating retinitis pigmentosa in a strain of zebrafish that undergoes photoreceptor degeneration similar to the human disease. Most of these drug candidates already have approval for use in humans, meaning that if they were found to be effective for treating retinitis pigmentosa, they could be fast-tracked for use in people. Zhang et al. found three compounds that helped photoreceptors survive both in zebrafish and in retinas grown in the laboratory derived from a mouse strain with degeneration similar to retinitis pigmentosa. Tests to find out how these three compounds worked at the molecular level revealed that they interfered with a protein that can trigger cell death. The tests also found other promising compounds, many of which offered increased protection when combined in pairs. Worldwide there are between 1.5 and 2.5 million people with retinitis pigmentosa. With this disease, loss of vision happens slowly, so identifying drugs that could slow or stop the process could help many people. These results suggest that placing animal testing earlier in the drug discovery process could complement traditional target-based methods. The compounds identified here, and the information about how they work, could expand potential treatment research. The next step in this research is to test whether the drugs identified by Zhang et al. protect mammals other than mice from the degeneration seen in retinitis pigmentosa.