Causal inference using observational intensive care unit data: a scoping review and recommendations for future practice.

This scoping review focuses on the essential role of models for causal inference in shaping actionable artificial intelligence (AI) designed to aid clinicians in decision-making. The objective was to identify and evaluate the reporting quality of studies introducing models for causal inference in intensive care units (ICUs), and to provide recommendations to improve the future landscape of research practices in this domain. To achieve this, we searched various databases including Embase, MEDLINE ALL, Web of Science Core Collection, Google Scholar, medRxiv, bioRxiv, arXiv, and the ACM Digital Library. Studies involving models for causal inference addressing time-varying treatments in the adult ICU were reviewed. Data extraction encompassed the study settings and methodologies applied. Furthermore, we assessed reporting quality of target trial components (i.e., eligibility criteria, treatment strategies, follow-up period, outcome, and analysis plan) and main causal assumptions (i.e., conditional exchangeability, positivity, and consistency). Among the 2184 titles screened, 79 studies met the inclusion criteria. The methodologies used were G methods (61%) and reinforcement learning methods (39%). Studies considered both static (51%) and dynamic treatment regimes (49%). Only 30 (38%) of the studies reported all five target trial components, and only seven (9%) studies mentioned all three causal assumptions. To achieve actionable AI in the ICU, we advocate careful consideration of the causal question of interest, describing this research question as a target trial emulation, usage of appropriate causal inference methods, and acknowledgement (and examination of potential violations of) the causal assumptions.

Coronavirus disease tracheostomy complications: a scoping review.

BACKGROUND: Coronavirus disease 2019 increased the numbers of patients requiring prolonged mechanical ventilation, with a subsequent increase in tracheostomy procedures. Coronavirus disease 2019 patients are high risk for surgical complications. This review examines open surgical and percutaneous tracheostomy complications in coronavirus disease 2019 patients. METHODS: Medline and Embase databases were searched (November 2021), and the abstracts of relevant articles were screened. Data were collected regarding tracheostomy technique and complications. Complication rates were compared between percutaneous and open surgical tracheostomy. RESULTS: Percutaneous tracheostomy was higher risk for bleeding, pneumothorax and false passage. Surgical tracheostomy was higher risk for peri-operative hypoxia. The most common complication for both techniques was post-operative bleeding. CONCLUSION: Coronavirus disease 2019 patients undergoing tracheostomy are at higher risk of bleeding and peri-operative hypoxia than non-coronavirus disease patients. High doses of anti-coagulants may partially explain this. Reasons for higher bleeding risk in percutaneous over open surgical technique remain unclear. Further research is required to determine the causes of differences found and to establish mitigating strategies.

Distance from source of reward as a marker for extinction-induced "despair": modulation by the antidepressants clomipramine and citalopram.

Despair-related withdrawal behaviors are common symptoms of major depression (MD) and can be ascribed to a loss or absence of former rewarding events. Extinction of negatively reinforced escape behavior in the Morris Water Maze has been shown to induce despair-like behavior. A new animal model of depressive-like behavior is based on the extinction of positively reinforced behavior, which was shown to induce spatial avoidance of the former source of reward and biting of the operandum. Treatment with antidepressants attenuated these extinction-induced behaviors, suggesting that they reflect a depressive-like state. Here we present a methodological variation of this depression model. We employed an elongated operant chamber rather than a two-compartment procedure with the intent to establish a flowing gradient of withdrawal from the source of reward, rather than an all-or-none binary measure. Furthermore, instead of employing extinction of lever-pressing behavior, we applied a cued fixed-time food-delivery schedule. Sixty adult male Wistar rats (n=12/group) were trained to receive a food reward after appearance of a cue-light (fixed interval 90s) in an elongated Skinner-box of 72 cm length. Prior to extinction, the animals were treated for 9 days with either 7.5 or 10mg/kg of the tricyclic antidepressant clomipramine, 7.5 or 10mg/kg of the selective serotonin reuptake inhibitor (SSRI) citalopram or vehicle. Subsequent testing in an open field was carried out to investigate potential effects of the antidepressants on locomotor- and anxiety-like behavior. An overall increase in distance from the feeder and biting behavior was found over the course of the extinction trials. Both, citalopram and clomipramine decreased the distance from the pellet feeder during the initial extinction trials compared to the vehicle-treated group. The attenuation of withdrawal behavior by the antidepressants supports the hypothesis that avoidance/withdrawal behavior during extinction trials can serve as a marker for extinction-induced depression and suggests the utility of this paradigm as a rodent model of depression.

Antidepressants reduce extinction-induced withdrawal and biting behaviors: a model for depressive-like behavior.

The withholding of expected rewards results in extinction of behavior and, hypothetically, to depression-like symptoms. In a test of this hypothesis, we examined the effects of extinction of food-reinforced lever-pressing on collateral behaviors that might be indices of depression. Operant extinction is known to be aversive to the organism and results in avoidance behavior. We hypothesized that avoidance of, or withdrawal from, the former source of reward may serve as a marker for "despair." Adult male Wistar rats (n=6-7 animals per group) were exposed to a Skinner box attached to a second compartment of the same size, providing opportunity for the animals to leave the operant chamber and to enter the "withdrawal" compartment. The animals spent a portion of the time during the extinction trials in this second chamber. To assess the predictive validity of this behavior as a potential marker of "despair," we tested the effects of chronic administration of two common antidepressant drugs on this measure. The tricyclic antidepressant imipramine (20 mg/kg) as well as the selective serotonin reuptake inhibitor citalopram (20 mg/kg) reduced the number of entries and time spent in the withdrawal compartment. We propose that entries into and time spent in the withdrawal compartment may operationalize "avoidance," a core symptom of major depression. Rearing as well as biting behaviors during the extinction trials were also attenuated by the antidepressant treatment. These results lend support to the hypothesis that extinction of positively reinforced operants evokes behaviors that reflect elements of "despair/depression" because these behaviors are modulated by antidepressant treatment. The avoidance of the operant chamber as a consequence of extinction, together with rearing and biting behaviors, may serve as useful measures for the testing of antidepressant treatments.

Attenuating effects of testosterone on depressive-like behavior in the forced swim test in healthy male rats.

The androgenic steroid testosterone is well known for its function in reproduction, sexual differentiation and sexual behavior. A growing number of human and animal studies suggest a modulatory role of testosterone in the regulation of emotionality and associated psychiatric disorders, including depressive-like disorders. However, most of the studies have been carried out in subjects deficient in androgenic steroid levels. Here, we tested potential beneficial effects of subcutaneously applied testosterone on emotionality and depressive-like behavior in healthy male rats. For this purpose, male Wistar rats (3-4 months) received either vehicle or testosterone (1.0, 2.0, 4.0mg/kg) subcutaneously and were tested for potential effects on motor activity and anxiety-like behavior in a novel open field and elevated plus-maze. The forced swim test was used for assessing potential beneficial effects of testosterone on depressive-like behavior. The results show, that, while subcutaneous application of testosterone failed to influence spontaneous motor activity as well as anxiety-like behavior in the open field, a trend for an increase in the time spent on the open arms in the elevated plus-maze with the highest dose was found. Furthermore, in the forced swim test, testosterone application induced a dose-dependent reduction of immobility behavior, indicating antidepressant-like action of testosterone in healthy animals.