Restricted Polypharmacy Compared to Usual Care in Mechanically Ventilated Patients: A Retrospective Cohort Study.

BACKGROUND: Adverse effects of excessive sedation in critically ill mechanically ventilated patients are well described. Although guidelines strongly recommend minimizing sedative use, additional agents are added as infusions, often empirically. The tradeoffs associated with such decisions remain unclear. METHODS: To test the hypothesis that a pragmatic propofol-based sedation regimen with restricted polypharmacy (RP; ie, prohibits additional infusions unless a predefined propofol dosage threshold is exceeded) would increase coma-and ventilator-free days compared with usual care (UC), we performed a retrospective cohort study of adults admitted to intensive care units (ICUs) of a tertiary-level medical center who were mechanically ventilated, initiated on propofol infusion, and had >50% probability of need for continued ventilation for the next 24 hours. We compared RP to UC, adjusting for baseline and time-varying confounding (demographics, care unit, calendar time of admission, vitals, laboratories, other interventions such as vasopressors and fluids, and more) through inverse probability weighting in a target trial framework. Ventilator-free days and coma-free days within 30 days of intubation and in-hospital mortality were the outcomes of interest. RESULTS: A total of 7974 patients were included in the analysis, of which 3765 followed the RP strategy until extubation. In the full cohort under UC, mean coma-free days were 23.5 (95% confidence interval [CI], [23.3-23.7]), mean ventilator-free days were 20.6 (95% CI, [20.4-20.8]), and the in-hospital mortality rate was 22.0% (95% CI, [21.2-22.8]). We estimated that an RP strategy would increase mean coma-free days by 1.0 days (95% CI, [0.7-1.3]) and ventilator-free days by 1.0 days (95% CI, [0.7-1.3]) relative to UC in our cohort. Our estimate of the confounding-adjusted association between RP and in-hospital mortality was uninformative (-0.5%; 95% CI, [-3.0 to 1.9]). CONCLUSIONS: Compared with UC, RP was associated with more coma- and ventilator-free days. Restricting addition of adjunct infusions to propofol may represent a viable strategy to reduce duration of coma and mechanical ventilation. These hypothesis-generating findings should be confirmed in a randomized control trial.

Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID-19 patients: A retrospective cohort study.

BACKGROUND: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium. METHODS: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels. RESULTS: A total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP. CONCLUSION: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium. IMPLICATION STATEMENT: PP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.

Delaying initiation of diuretics in critically ill patients with recent vasopressor use and high positive fluid balance.

BACKGROUND: Fluid overload is associated with poor outcomes. Clinicians might be reluctant to initiate diuretic therapy for patients with recent vasopressor use. We estimated the effect on 30-day mortality of withholding or delaying diuretics after vasopressor use in patients with probable fluid overload. METHODS: This was a retrospective cohort study of adults admitted to ICUs of an academic medical centre between 2008 and 2012. Using a database of time-stamped patient records, we followed individuals from the time they first required vasopressor support and had >5 L cumulative positive fluid balance (plus additional inclusion/exclusion criteria). We compared mortality under usual care (the mix of care actually delivered in the cohort) and treatment strategies restricting diuretic initiation during and for various durations after vasopressor use. We adjusted for baseline and time-varying confounding via inverse probability weighting. RESULTS: The study included 1501 patients, and the observed 30-day mortality rate was 11%. After adjusting for observed confounders, withholding diuretics for at least 24 h after stopping most recent vasopressor use was estimated to increase 30-day mortality rate by 2.2% (95% confidence interval [CI], 0.9-3.6%) compared with usual care. Data were consistent with moderate harm or slight benefit from withholding diuretic initiation only during concomitant vasopressor use; the estimated mortality rate increased by 0.5% (95% CI, -0.2% to 1.1%). CONCLUSIONS: Withholding diuretic initiation after vasopressor use in patients with high cumulative positive balance (>5 L) was estimated to increase 30-day mortality. These findings are hypothesis generating and should be tested in a clinical trial.

Door-to-Needle Delays in Minor Stroke: A Causal Inference Approach.

BACKGROUND AND PURPOSE: Thrombolysis rates among minor stroke (MS) patients are increasing because of increased recognition of disability in this group and guideline changes regarding treatment indications. We examined the association of delays in door-to-needle (DTN) time with stroke severity. METHODS: We performed a retrospective analysis of all stroke patients who received intravenous tissue-type plasminogen activator in our emergency department between July 1, 2011, and February 29, 2016. Baseline characteristics and DTN were compared between MS (National Institutes of Health Stroke Scale score ≤5) and nonminor strokes (National Institutes of Health Stroke Scale score >5). We applied causal inference methodology to estimate the magnitude and mechanisms of the causal effect of stroke severity on DTN. RESULTS: Of 315 patients, 133 patients (42.2%) had National Institutes of Health Stroke Scale score ≤5. Median DTN was longer in MS than nonminor strokes (58 versus 53 minutes; P=0.01); fewer MS patients had DTN ≤45 minutes (19.5% versus 32.4%; P=0.01). MS patients were less likely to use emergency medical services (EMS; 62.6% versus 89.6%, P<0.01) and to receive EMS prenotification (43.9% versus 72.4%; P<0.01). Causal analyses estimated MS increased average DTN by 6 minutes, partly through mode of arrival. EMS prenotification decreased average DTN by 10 minutes in MS patients. CONCLUSIONS: MS had longer DTN times, an effect partly explained by patterns of EMS prenotification. Interventions to improve EMS recognition of MS may accelerate care.

Effects of parental childhood cultural health environment on children's influenza and COVID-19 vaccination status.

Most studies examining factors associated with pediatric influenza (flu) and coronavirus disease (COVID-19) vaccination uptake focus on parental demographics. We examined whether the childhood cultural health environment (CHE) of parents (measured by self-reported regular attendance at doctor and dentist visits during childhood) was associated with flu and COVID-19 vaccination of their children. Using 2023 survey data from 397 US parents and causal inference methods, we estimated the average causal effect of parental CHE on flu vaccination rates (0.16 [95 % confidence interval: 0.06,0.27]) and COVID-19 (0.14 [95 % confidence interval: 0.04,0.24]), indicating that if all parents had attended regular doctor/dentist visits as children, flu and COVID-19 vaccination rates in children would be 16 % and 14 % higher, respectively, than if none had. Our findings suggest that early life exposure to medical and dental care has significant and lasting effects on the health of individuals and families.

Is Deep Reinforcement Learning Ready for Practical Applications in Healthcare? A Sensitivity Analysis of Duel-DDQN for Hemodynamic Management in Sepsis Patients.

The potential of Reinforcement Learning (RL) has been demonstrated through successful applications to games such as Go and Atari. However, while it is straightforward to evaluate the performance of an RL algorithm in a game setting by simply using it to play the game, evaluation is a major challenge in clinical settings where it could be unsafe to follow RL policies in practice. Thus, understanding sensitivity of RL policies to the host of decisions made during implementation is an important step toward building the type of trust in RL required for eventual clinical uptake. In this work, we perform a sensitivity analysis on a state-of-the-art RL algorithm (Dueling Double Deep Q-Networks) applied to hemodynamic stabilization treatment strategies for septic patients in the ICU. We consider sensitivity of learned policies to input features, embedding model architecture, time discretization, reward function, and random seeds. We find that varying these settings can significantly impact learned policies, which suggests a need for caution when interpreting RL agent output.

Birth month affects lifetime disease risk: a phenome-wide method.

OBJECTIVE: An individual's birth month has a significant impact on the diseases they develop during their lifetime. Previous studies reveal relationships between birth month and several diseases including atherothrombosis, asthma, attention deficit hyperactivity disorder, and myopia, leaving most diseases completely unexplored. This retrospective population study systematically explores the relationship between seasonal affects at birth and lifetime disease risk for 1688 conditions. METHODS: We developed a hypothesis-free method that minimizes publication and disease selection biases by systematically investigating disease-birth month patterns across all conditions. Our dataset includes 1 749 400 individuals with records at New York-Presbyterian/Columbia University Medical Center born between 1900 and 2000 inclusive. We modeled associations between birth month and 1688 diseases using logistic regression. Significance was tested using a chi-squared test with multiplicity correction. RESULTS: We found 55 diseases that were significantly dependent on birth month. Of these 19 were previously reported in the literature (P < .001), 20 were for conditions with close relationships to those reported, and 16 were previously unreported. We found distinct incidence patterns across disease categories. CONCLUSIONS: Lifetime disease risk is affected by birth month. Seasonally dependent early developmental mechanisms may play a role in increasing lifetime risk of disease.