A Population-Based Test-Negative Matched Case-Control Analysis of SARS-CoV-2 Vaccine Effectiveness Among Pregnant People in Ontario, Canada.

OBJECTIVE: Pregnancy is a risk factor for severe SARS-CoV-2 infection, which can result in adverse pregnancy outcomes, thus making understanding vaccine effectiveness (VE) in this population important. This study aimed to assess the VE of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in pregnant people. METHODS: Population-based matched test-negative case-control study of pregnant people aged 18-49 years, of 12 or more weeks gestation in Ontario, Canada, symptomatic with possible SARS-CoV-2 infection, and having at least 1 positive (n = 1842) or negative (n = 8524) real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 test between December 14, 2020, and December 31, 2021. The exposure was receipt of ≥1 dose of mRNA COVID-19 vaccine versus no vaccination. Exposure was further stratified by number and recency of doses. The primary outcome was a positive SARS-CoV-2 RT-PCR test. As a secondary outcome, VE for COVID-19-related hospitalization was assessed. RESULTS: In the primary outcome analysis, there were 1821 positive cases, matched to 1821 negative controls. The mean (SD) maternal age was 31 (5) years. When compared to those unvaccinated, receipt of ≥1 dose was associated with an estimated VE of 39% (95% CI 29%-48%) for symptomatic infection, and 85% (95% CI 72%-92%) for COVID-19 hospitalization. VE estimates demonstrated waning with increased time since last vaccination. CONCLUSIONS: mRNA COVID-19 vaccines provide protection against symptomatic COVID-19 illness and are highly effective at preventing severe illness in pregnant people. The observed effect of vaccine waning highlights the importance of booster doses to provide optimal protection for pregnant people.

Twin pregnancy and severe maternal mental illness: a Canadian population-based cohort study.

Twin pregnancy is a risk factor for postpartum depression and anxiety. Whether this translates into a higher risk of severe maternal mental illness in the short-term or long-term is unknown. This study was a population-based retrospective cohort study, using linked health administrative databases for the entire province of Ontario, Canada. Included were primiparas aged 15-50 years with a twin vs. singleton hospital livebirth, between January 1, 2003, and March 31, 2019. Propensity-score inverse probability of treatment weights accounted for potential confounding. The primary outcome of severe mental illness comprised a composite of an emergency department visit or hospitalization for mental illness or self-injury, or death by suicide, assessed in the first year after birth, and in long-term follow-up, up to 17 years thereafter. Fifteen thousand twenty-four twin and 796,804 (15,022 weighted) singleton births were included, with a mean (IQR) duration of follow-up of 9 (5-13) years. After weighting, the mean (SD) maternal age was 31.3 (5.5) years. In the first 365 days postpartum, severe mental illness occurred at rates of 10.5 and 8.7 per 1000 person-years in twin and singleton mothers, respectively, corresponding to a hazard ratio (HR) of 1.21 (95% CI 1.07-1.47). From 366 days onward, the corresponding figures were 5.9 and 6.1 per 1000 person-years (HR 0.96, 95% CI 0.89-1.04). Individuals with a twin birth appear to experience an increased risk for severe mental illness in the first year postpartum, but not thereafter. This suggests a potential need for targeted counselling and mental health services for mothers within the first year after birth.

Timing of Antenatal Corticosteroids for Optimal Neonatal Outcomes: A Markov Decision Analysis Model.

OBJECTIVE: Antenatal corticosteroids (ACSs) are administered to pregnant individuals at high risk of preterm delivery to reduce neonatal morbidity and mortality. ACSs have a limited timeframe of effectiveness, and timing of administration can be difficult because of uncertainty surrounding the likelihood of preterm delivery. The objective of the current study was to design a decision analysis model to optimize the timing of ACS administration and identify important model variables that impact administration timing preference. METHODS: We created a Markov decision analysis model with a base case of a patient at 240 weeks gestation with antepartum hemorrhage. Decision strategies included immediate, delayed, and no ACS administration. Outcomes were based on the neonatal perspective and consisted of lifetime quality adjusted life years (QALYs). Data for model inputs were derived from current literature and clinical recommendations. RESULTS: Our base case analysis revealed a preferred strategy of delaying ACSs for 2 weeks, which maximized QALYs (39.18 lifetime discounted), driven by reduced neonatal morbidity at the expense of 0.1% more neonatal deaths, when compared with immediate ACS administration. Sensitivity analyses identified that, if the probability of delivery within the next week was >6.19%, then immediate steroids were preferred. Other important variables included gestational age, ACS effectiveness, and ACS adverse effects. CONCLUSION: ACS timing involves a trade-off between morbidity and mortality, and optimal timing depends on probability of delivery, gestational age, and risks and benefits of ACSs. Clinicians should carefully consider these factors prior to ACS administration.

Special Populations: Disaster Care Considerations in Chronically Ill, Pregnant, and Morbidly Obese Patients.

Special populations, which include the morbidly obese and patients with chronic, complex medical conditions that require long-term health care services and infrastructure, are at increased risk for morbidity and mortality when these services are disrupted during a disaster. Past experiences have identified significant challenges in restoring necessary care services to these patients following major environmental events. This article describes the impact of disasters on special populations, provides a framework for future disaster preparation and planning, and identifies areas in need of further research. Gravid patients, who are often overlooked in disaster planning and preparation, are also discussed.

Analgesic, sedative, antipsychotic, and neuromuscular blocker use in Canadian intensive care units: a prospective, multicentre, observational study.

PURPOSE: Our aim was to describe analgo-sedation and antipsychotic and neuromuscular blocking drug (NMBD) use in critically ill patients, management strategies, and variables associated with these practice patterns. METHODS: This prospective observational study in 51 intensive care units (ICUs) included all patients who underwent invasive mechanical ventilation (MV) over a two-week period during 2008-2009. RESULTS: We included 712 patients representing 3,620 patient-days. Median MV duration was 3.0 days (interquartile range 2-6). During MV, 92% of patients received analgo-sedation, 32% an adjunct agent (e.g., acetaminophen), 18% NMBDs, and 10% antipsychotics. Opioids were used more frequently than benzodiazepines or propofol (84.8% vs 62.2% vs 10.1% patients, respectively, P < 0.0001). Independent predictors of opioid and benzodiazepine use were a longer MV duration, assessment scales, physical restraints, and university-affiliated hospital. Although more than 50% of ICUs reported that assessment tools, protocols, and daily sedation interruption (DSI) were available for use, application was modest: sedation scale 53.0%, pain scale 19.1%, delirium scale 5.2%, protocol 25.0%, DSI 42.1%. Accidental device removal occurred in 4.6% of patients, with 75.8% of events during DSI. Daily sedation interruption was associated with protocol use, physical restraints, university-affiliated hospital, and short-duration MV. Variables associated with protocol use included assessment scales, longer MV duration, lack of physical restraints, and admission to a community hospital. CONCLUSION: Nearly all MV patients received analgo-sedation. Opioids were used more often than sedatives despite infrequent use of pain scales. Few patients received antipsychotic therapy, but physical restraint was common. Protocol use was poor compared to DSI. Duration of MV predicted the use of either.

Predictors of physical restraint use in Canadian intensive care units.

INTRODUCTION: Physical restraint (PR) use in the intensive care unit (ICU) has been associated with higher rates of self-extubation and prolonged ICU length of stay. Our objectives were to describe patterns and predictors of PR use. METHODS: We conducted a secondary analysis of a prospective observational study of analgosedation, antipsychotic, neuromuscular blocker, and PR practices in 51 Canadian ICUs. Data were collected prospectively for all mechanically ventilated adults admitted during a two-week period. We tested for patient, treatment, and hospital characteristics that were associated with PR use and number of days of use, using logistic and Poisson regression respectively. RESULTS: PR was used on 374 out of 711 (53%) patients, for a mean number of 4.1 (standard deviation (SD) 4.0) days. Treatment characteristics associated with PR were higher daily benzodiazepine dose (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.00 to 1.11), higher daily opioid dose (OR 1.04, 95% CI 1.01 to 1.06), antipsychotic drugs (OR 3.09, 95% CI 1.74 to 5.48), agitation (Sedation-Agitation Scale (SAS) >4) (OR 3.73, 95% CI 1.50 to 9.29), and sedation administration method (continuous and bolus versus bolus only) (OR 3.09, 95% CI 1.74 to 5.48). Hospital characteristics associated with PR indicated patients were less likely to be restrained in ICUs from university-affiliated hospitals (OR 0.32, 95% CI 0.17 to 0.61). Mainly treatment characteristics were associated with more days of PR, including: higher daily benzodiazepine dose (incidence rate ratio (IRR) 1.07, 95% CI 1.01 to 1.13), daily sedation interruption (IRR 3.44, 95% CI 1.48 to 8.10), antipsychotic drugs (IRR 15.67, 95% CI 6.62 to 37.12), SAS <3 (IRR 2.62, 95% CI 1.08 to 6.35), and any adverse event including accidental device removal (IRR 8.27, 95% CI 2.07 to 33.08). Patient characteristics (age, gender, Acute Physiology and Chronic Health Evaluation II score, admission category, prior substance abuse, prior psychotropic medication, pre-existing psychiatric condition or dementia) were not associated with PR use or number of days used. CONCLUSIONS: PR was used in half of the patients in these 51 ICUs. Treatment characteristics predominantly predicted PR use, as opposed to patient or hospital/ICU characteristics. Use of sedative, analgesic, and antipsychotic drugs, agitation, heavy sedation, and occurrence of an adverse event predicted PR use or number of days used.

Use of sedation and neuromuscular blockers in critically ill adults receiving high-frequency oscillatory ventilation.

BACKGROUND: Nearly all patients receive sedation and neuromuscular blockers (NMBs) during high-frequency oscillatory ventilation (HFOV). OBJECTIVE: To describe analgo-sedation and NMB use prior to and during HFOV in adults with acute respiratory distress syndrome. METHODS: Retrospective single-center study of 131 consecutive adults whose care was managed with HFOV from 2002 to 2011. RESULTS: During the first 4 days of HFOV, 89% and 95% of patients received sedation and opioids, respectively. Upon HFOV initiation, 119 (90.8%) patients received fentanyl doses higher than 200 µg/h; of these, 48 also received more than 20 mg/h of midazolam. Analgo-sedation doses increased significantly over time such that doses were double by day 3. Factors independently associated with fentanyl doses higher than 200 µg/h were NMB ever used (OR 4.43; 95% CI 1.26-15.65, p = 0.02), pH less than 7.15 (OR 2.08; 95% CI 1.22-3.5, p = 0.007), worsening partial pressure of oxygen/fraction of inspired oxygen (OR 1.05; 95% CI 1.00-1.10, p = 0.04), and Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR 0.87; 95% CI 0.79-0.97, p = 0.009). Deep sedation was commonly administered when NMBs were not being used, with 99.2% of sedation-agitation scores of 1 or 2. Eighty-six patients (65.6%) received NMBs and use was greatest on day 1 (59.5%). Train-of-Four was measured every hour for 53.4% of patients; 29.2% of the measurements were 0 of 4. NMB use declined over the 10-year study period. CONCLUSIONS: High analgo-sedation doses were associated with APACHE II scores, worsening gas exchange, and NMB use. Two thirds of patients received NMBs; use was highest on day 1 and subsequently declined. The percentage of patients who received NMB during HFOV in our study was lower than that previously reported. Future research should evaluate patient outcomes with and without use of NMBs, as well as the potential to manage patients with less sedation.