Impact of extended-infusion piperacillin-tazobactam in a Canadian community hospital.

Background: Studies have demonstrated improved clinical outcomes with extended infusion (EI) piperacillin/tazobactam (TZP) compared to standard infusion (SI). However, there is less evidence on its benefits in noncritically-ill patients. Hospital-wide EI TZP was implemented at our site on February 21, 2012. Our objectives were to compare clinical, safety and economic outcomes between EI and SI TZP. Methods: A retrospective cohort study of all adult patients who received EI TZP (3.375 g IV q8h infused over 4 hours and SI TZP for ≥ 48 hours during 3 years pre-and postimplementation was conducted. The primary study outcome was 14-day mortality while secondary outcomes included length of hospital stay (LOS), nursing plus pharmacy cost, occurrence of Clostridioides difficile infection, readmission within 30 days and change in Pseudomonas aeruginosa minimum inhibitory concentration (MIC) distribution for TZP. The primary outcome and binary secondary outcomes were analyzed using a logistic regression model. LOS was examined using time to event analysis. Cost was examined using linear regression modelling. Results: Overall, 2034 patients received EI TZP and 1364 patients received SI TZP. EI TZP was associated with lower odds of mortality (OR 0.76, 95% CI 0.63-0.91), lower odds of C. difficile infection (OR 0.59, 95% CI 0.41-0.84) and 8% lower cost (estimate 0.92, 95% CI 0.87-0.98) compared to SI TZP. Conclusions: Hospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of C. difficile infection with cost savings at our institution.

Peri-Operative Wearables in Elder Recover after Surgery (POWERS) study: a protocol for a multicentre, prospective cohort study to evaluate perioperative activity with postoperative disability in older adults after non-cardiac surgery.

INTRODUCTION: The ageing population has led to an increasing proportion of surgical patients with greater frailty and comorbidity. Complications and mortality within 30 days of a surgical procedure are often used to evaluate success in the perioperative period however these measures can potentially underestimate a substantial level of morbidity associated with surgery. Personal wearable technologies are now readily available and can offer detailed information on activity intensity, sedentary behaviour and sleeping patterns. These devices may provide important information perioperatively by acting as a non-invasive, and cost-efficient means to risk stratify patients. METHODS AND ANALYSIS: The Peri-Operative Wearables in Elder Recover After Surgery (POWERS) study is a multicentre observational study of 200 older adults (≥65 years) having major elective non-cardiac surgery. The objectives are to characterise the association between preoperative and postoperative activity monitor measurements with postoperative disability and recovery, as well as characterise trajectories of activity and sleep in the perioperative period. Activity will be monitored with the ActiGraph GT3X device and measured for 7-day increments, preoperatively, and at 1 week, 1 month and 3 months postoperatively. Disability will be assessed using the WHO Disability Assessment Schedule 2.0 assessed at 1 week, 1 month and 3 months postoperatively. ETHICS AND DISSEMINATION: The POWERS study received research ethics board approval at all participating sites on 1 August 2019 (REB # 19-121 (CTO 1849)). Renewal was granted on 19 May 2022.

The Effect of Time to Treatment With Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Examining the association of time to treatment (drug or placebo) with survival to hospital discharge and neurologic outcome. DESIGN: Post hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo randomized controlled trial. SETTING: Emergency medical services enrolled patients with out-of-hospital cardiac arrest (OHCA) at multiple North American sites. PATIENTS: Adults with nontraumatic OHCA and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia refractory to at least one defibrillation attempt were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used logistic regression to examine the association of time to treatment with survival to hospital discharge and favorable neurologic status at discharge (modified Rankin Scale ≤ 3) for the three treatment groups including an interaction term between treatment and time to treatment to determine the effect of time on treatment effects. Time to treatment data were available for 2,994 out of 3,026 patients (99%). The proportion of patients who survived to hospital discharge decreased as time to drug administration increased, in amiodarone (odds ratio [OR], 0.91; 95% CI, 0.90-0.93 per min), lidocaine (OR, 0.93; 95% CI, 0.91-0.96), and placebo (OR, 0.91; 95% CI, 0.90-0.93). Comparing amiodarone to placebo, there was improved survival at all times of drug administration (OR, 1.32; 95% CI, 1.05-1.65). Comparing lidocaine to placebo, survival was not different with shorter times to drug administration (< 11 min), whereas survival was higher with lidocaine at longer times to drug administration with an interaction between treatment effect and time to treatment (p = 0.048). Survival with good neurologic outcome showed similar results for all analyses. CONCLUSIONS: Survival and favorable neurologic outcomes decreased with longer times to drug administration. Amiodarone improved survival at all time points whereas lidocaine improved survival only at later time points, compared with placebo.

Patient-Reported Outcomes After Tetralogy of Fallot Repair.

BACKGROUND: Comprehensive assessment of tetralogy of Fallot (TOF) outcomes extends beyond morbidity and mortality to incorporate patient-reported outcomes (PROs), including quality of life (QOL) and health status (HS). OBJECTIVES: This study explored PROs in adolescents and adults with TOF and delineated variables associated with PROs. METHODS: This was a cross-sectional observational study within a larger prospective registry of adolescents and adults with repaired TOF and moderate or greater pulmonary regurgitation from North America, Europe, and Asia. Participants completed PROs, including a QOL linear analogue scale (QOL-LAS) and an HS visual analogue scale (HS-VAS). Scores were classified according to age cohorts: <18, 18 to 25, 26 to 40, and >40 years. RESULTS: The study included 607 patients (46.3% female; median age 28.5 years). Median QOL-LAS scores (0-100) were similar across age cohorts (85, 80, 80, 80; P = 0.056). Median HS-VAS scores (0-100) were lowest for the oldest cohort (77) compared with the 3 younger cohorts (85, 80, 80) (P = 0.004). With advancing age, there were increased reports of poor mobility (P < 0.001) and pain or discomfort (P = 0.004); problems in these dimensions were reported by 19.1% and 37.2% of patients aged >40 years, respectively. Of factors associated with superior PROs on multivariable regression modeling (ie, being White, being nonsyndromic, having employment, and having better left ventricular function; P < 0.05), asymptomatic status (functional class I) was the variable associated with the greatest number of QOL and HS measures (P < 0.001). CONCLUSIONS: Strategies to improve TOF outcomes should consider PROs alongside conventional clinical variables. Factors associated with poorer PROs represent opportunities to intervene to improve the lives of patients with TOF.

Mental Health Trajectories of Children and Caregivers Using School-Based Health Centers During the COVID-19 Pandemic.

INTRODUCTION: This was a prospective study of children registered at school-based health centers (SBHCs) in Canada. The objectives were to compare mental health trajectories of children and parents/caregivers who accessed SBHCs during the pandemic relative to those who did not. METHOD: Parents/caregivers of children who attended SBHCs completed the Strengths and Difficulties Questionnaire (SDQ) and the Generalized Anxiety Disorder-7 (GAD-7) at three time points during the pandemic. The primary analysis used linear mixed models to examine the relationship between SBHC visits during the pandemic and children's SDQ score trajectories. The secondary analysis was the same for parents'/caregivers' GAD-7 scores. RESULTS: There were 435 children included. SDQ and GAD-7 scores worsened over time for children and parents/caregivers who attended SBHCs during the pandemic compared to those who did not. DISCUSSION: Children and parents/caregivers with worsening mental health symptoms may have sought care at SBHCs since they were accessible during the pandemic.

Clinical tools to assess functional capacity before elective non-cardiac surgery: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map the evidence on clinical tools to assess functional capacity prior to elective non-cardiac surgery. INTRODUCTION: Functional capacity is a strong prognostic indicator before surgery, which can be used to identify patients at elevated risk of postoperative complications, yet, there is no consensus on which clinical tools should be used to assess functional capacity in patients prior to non-cardiac surgery. INCLUSION CRITERIA: This review will consider any randomized or non-randomized studies that evaluate the performance of a functional capacity assessment tool in adults (≥18 years) prior to non-cardiac surgery. For studies to be included, the tool must be used clinically for risk stratification. We will exclude studies on lung and liver transplant surgery, as well as ambulatory procedures performed under local anesthesia. METHODS: The review will be conducted in line with the JBI methodology for scoping reviews. A peer-reviewed search strategy will be used to query relevant databases (ie, MEDLINE, Embase, EBM Reviews). Additional sources of evidence will include databases of non-peer-reviewed literature and the reference lists of included studies. Two independent reviewers will identify eligible studies in 2 stages: stage 1, based on titles and abstracts; and stage 2, based on full texts. Information on study details, measurement properties, pragmatic qualities, and/or clinical utility metrics will be charted in duplicate onto standardized data collection forms. The results will be presented using descriptive summaries, frequency tables, and visual plots that highlight the extent of evidence and remaining gaps in the validation process of each tool. REVIEW REGISTRATION: Open Science Framework https://osf.io/6nfht.

In-hospital mortality for aspiration pneumonia in a tertiary teaching hospital: A retrospective cohort review from 2008 to 2018.

BACKGROUND: Aspiration pneumonia is a preventable condition that has higher rates of recurrence and mortality compared to non-aspiration pneumonia. The primary objective of the study was to examine independent patient factors that are associated with mortality in those requiring acute admission for aspiration pneumonia at a tertiary institution. Secondary goals of the study were to review whether factors such as mechanical ventilation and speech language pathology intervention can impact patient mortality, length of stay (LOS), and costs relating to hospitalization. METHODS: Patients older than 18 years of age who were admitted with a primary diagnosis of aspiration pneumonia from January 1, 2008 to December 31, 2018 at Unity Health Toronto-St. Michael's hospital in Toronto, Canada, were included in the study. Descriptive analyses were performed on patient characteristics using age as a continuous variable as well as a dichotomous variable with age 65 as a cut-off. Multivariable logistic regression was used to identify independent factors that contributed to in-hospital mortality and Cox proportional-hazard regression was used to identify independent factors that affected LOS. RESULTS: A total of 634 patients were included in this study. 134 (21.1%) patients died during hospitalization with an average age of 80.3 ± 13.4. The in-hospital mortality did not change significantly over the ten-year period (p = 0.718). Patients who died had longer LOS with a median length of 10.5 days (p = 0.012). Age [Odds Ratio (OR) 1.72, 95% Confidence Interval (95% CI) 1.47-2.02, p < 0.05] and invasive mechanical ventilation (OR 2.57, 95% CI 1.54-4.31, p < 0.05) were independent predictors of mortality while female gender was found to be a protective factor (OR 0.60, 95% CI 0.38-0.92, p = 0.02). Elderly patients had five times higher risk of dying during their hospital course when compared to younger patients [Hazard Ratio (HR) 5.25, 95% CI 2.99-9.23, p < 0.05). CONCLUSION: Elderly patients are a high-risk population for developing aspiration pneumonia and are at higher risk of death when hospitalized for this condition. This warrants improved preventative strategies in the community. Further studies involving other institutions and creating a Canada-wide database are required.

Subjective and objective evaluation of corneal haze after accelerated corneal crosslinking for corneal ectasias.

PURPOSE: To evaluate the relationship between subjective (slit lamp examination [SLE]) and objective (densitometry) measurements of corneal haze after accelerated corneal crosslinking (aCXL), assess the relationship between densitometry and corrected distance visual acuity (CDVA), and determine the effect of baseline characteristics on densitometry after aCXL in eyes with progressive keratoconus and other ectasias. SETTING: Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada. DESIGN: Retrospective analysis of a prospective interventional cohort study. METHODS: Scheimpflug-derived corneal densitometry, CDVA, maximum keratometry (Kmax ), and central corneal thickness were measured preoperatively and up to 1 year after aCXL, and post-operative haze was estimated with SLE (n = 483 eyes). A random effect model was used to examine the relationship between post-operative subjective haze with SLE and densitometry. Linear mixed models were used to examine the relationship between densitometry, pre-operative baseline characteristics, and CDVA. RESULTS: There was a significant association between subjective haze with SLE and densitometry (p < 0.001). There was a significant relationship between CDVA and densitometry: for every 10 GSUs of increased densitometry in the 0-2 mm zone, CDVA worsened by approximately half a Snellen line (p < 0.001). Age and pre-operative Kmax were significant predictors of densitometry. For every 10 years of age, densitometry increased by 0.68 GSUs (95% CI [0.27 to 1.07], p < 0.001). For every 10 D of increased preoperative Kmax , densitometry increased by 0.69 GSUs (95% CI [0.41 to 0.98], p < 0.001). CONCLUSIONS: Subjective haze after aCXL estimated with SLE, is significantly associated with densitometry. Increased densitometry after aCXL is associated with a reduction in CDVA.

Body Weight at Age Four Years and Readiness to Start School: A Prospective Cohort Study.

Background: Adolescents with obesity have lower academic performance, but little is known about the association between body weight in early childhood and school readiness. The objective was to examine the association between age- and sex-standardized body mass index (zBMI) and body weight status and school readiness in young children. Methods: A prospective cohort study in Toronto, Canada, was conducted in young children enrolled in TARGet Kids!. Children's weight and height were measured before the start of kindergarten. Children's school readiness was measured by the Early Development Instrument (EDI), a validated teacher-completed instrument that assesses children's skills and behaviors in five developmental domains in kindergarten. Generalized estimating equations, adjusted for relevant confounders, were used in the analysis. Results: The study included 1015 children (1217 observations): 52% were male and mean age at zBMI was 4.2 years [50 months (SD 12.1)] and school readiness was 5.2 years [62.7 months (SD 6.9)]. There was no evidence found that zBMI was associated with school readiness. However, in a post hoc analysis, being classified as overweight or with obesity in kindergarten was associated with twofold higher odds of vulnerability in school readiness and a lower social competence score compared with their normal weight peers. Conclusions: Being classified as overweight or with obesity was associated with poor school readiness in year 2 of kindergarten. Early interventions to promote healthy growth before school entry may help promote development and school readiness in young children. www.clinicaltrials.gov (NCT01869530).

Ontario Cataract Quality Outcome Initiative: appropriateness and prioritization of cataract surgery.

OBJECTIVE: To explore the utility of the Catquest 9SF visual function (VF) questionnaire along with visual acuity (VA) for determining appropriateness and priority for cataract surgery. To evaluate the feasibility of administering the Catquest-9SF in a clinical setting using web-based electronic data capture and interpretation. DESIGN: Prospective multicentred interventional observational study. PARTICIPANTS: Subjects undergoing sequential cataract surgery in both eyes at 4 sites in Ontario. METHODS: We recorded best-corrected VA (BCVA) and VA with current correction (CCVA) in each eye and both eyes (OU) and Catquest-9SF responses on a tablet before and after cataract surgery. Linear regression models were employed to test for associations between VA and visual function (VF). RESULTS: Preoperative BCVA and CCVA in the worse eye were significant predictors of change in VF (p = 0.006 and p = 0.008, respectively); subjects with worse VA had a greater improvement in VF after surgery. There was a significant association between improvement in VF and improvement in CCVA OU (p = 0.001). Fourteen of 151 subjects (9%) had no improvement or worse VF scores after surgery. Within this group, 10 of 14 subjects had a preoperative score ≤-3, which is suggestive of minimal visual disability. Within this subset, 4 of 14 subjects (2.6%) had a preoperative BCVA of 20/30 or better in their worse eye. CONCLUSIONS: For patient groups with equal VA, the Catquest-9SF score can help determine priority for surgery. Web-based data capture and interpretation allow for efficient virtual assessments of VF. A BCVA in the worse eye of 20/30 or better combined with a Catquest-9SF score <-3 can be used as a guideline for lowest priority.

Ophthalmic findings in marginally housed women in a Canadian city.

OBJECTIVE: To assess the prevalence and common causes of ocular pathology experienced by vulnerable women with marginalized housing and/or a history of abuse, violence, and trafficking. METHODS: Using a stratified random sampling technique, we recruited 93 women living in 10 randomly selected women's shelters in Toronto, Canada between May and November of 2018. All English-speaking females older than the age of 18 were eligible to participate. Data on demographics, medical or ocular history, subjective visual acuity, and access to eye care were obtained. Comprehensive visual screening and dilated fundoscopy were performed for each participant. RESULTS: The median age was 40 years (interquartile range, 30.5-54 years) and the median duration of homelessness was 8 months (interquartile range, 2.25-20.5 months); 63.4% of participants reported a history of abuse, 44.9% experienced head trauma, 15.9% experienced eye trauma, 22.5% identified as refugees, and 2.17% (2 of 92) had been victims of human trafficking. The above variables were not significantly related to vision problem severity on univariate analysis. Based on the presenting visual acuity, 27.8% of participants (95% CI [18.9-38.2]) were found to have visual impairment. Visual impairment was mainly related to refractive error (54.8% [51 of 93]), however, nonrefractive pathology was also observed. Of all the participants, 64.5% had one or more abnormal findings during the vision screening, and 40.9% needed follow-up by an ophthalmologist. Most participants (96.7%) expressed interest in accessing free eye examinations. CONCLUSIONS: Visual impairment is highly prevalent among homeless women living in Toronto. Routine vision-screening programs present an opportunity to improve the ocular health of this vulnerable population.

Effect of a tailored sepsis treatment protocol on patient outcomes in the Tikur Anbessa Specialized Hospital, Ethiopia: results of an interrupted time series analysis.

BACKGROUND: Despite improvement, sepsis mortality rates remain high, with an estimated 11 million sepsis-related deaths globally in 2017 (Rudd et. al, Lancet 395:200-211, 2020). Low- and middle-income countries (LMICs) are estimated to account for 85% of global sepsis mortality; however, evidence for improved sepsis mortality in LMICs is lacking. We aimed to improve sepsis care and outcomes through development and evaluation of a sepsis treatment protocol tailored to the Tikur Anbessa Specialized Hospital Emergency Department, Ethiopia, context. METHODS: We employed a mixed methods design, including an interrupted times series study, pre-post knowledge testing, and process evaluation. The primary outcome was the proportion of patients receiving appropriate sepsis care (blood culture collection before antibiotics and initiation of appropriate antibiotics within 1 h of assessment). Secondary outcomes included time to antibiotic administration, 72-h sepsis mortality, and 90-day all-cause mortality. Due to poor documentation, we were unable to assess our primary outcome and time to antibiotic administration. We used segmented regression with outcomes as binomial proportions to assess the impact of the intervention on mortality. Pre-post knowledge test scores were analyzed using the Student's t-test to compare group means for percentage of scenarios with correct diagnosis. RESULTS: A total of 113 and 300 patients were enrolled in the pre-implementation and post-implementation phases respectively. While age and gender were similar across the phases, a higher proportion (31 vs. 57%) of patients had malignancies in the post-implementation phase. We found a significant change in trend between the phases, with a trend for increasing odds of survival in the pre-implementation phase (OR 1.24, 95% CI 0.98-1.56), and a shift down, with odds of survival virtually flat (OR 0.95, 95% CI. 0.88-1.03) in the post-implementation phases for 72-h mortality, and trends for survival pre- and post-implementation are virtually flat for 90-day mortality. We found no significant difference in pre-post knowledge test scores, with interpretation limited by response rate. Implementation quality was negatively impacted by resource challenges. CONCLUSION: We found no improvement in sepsis outcomes, with a trend for increasing odds of survival lost post-implementation and no significant change in knowledge pre- and post-implementation. Variable availability of resources was the principal barrier to implementation. TRIAL REGISTRATION: Open Science Framework osf.io/ju4ga . Registered June 28, 2017.

Introducing the Safety Threats and Adverse events in Trauma (STAT) taxonomy: standardized classification system for evaluating safety during trauma resuscitation.

PURPOSE: Adverse events (AEs) during trauma resuscitation are common and heterogeneity in reporting limits comparisons between hospitals and systems. A recent modified Delphi study established a taxonomy of AEs that occur during trauma resuscitation. This tool was further refined to yield the Safety Threats and Adverse events in Trauma (STAT) taxonomy. The objective of this study was to evaluate the inter-rater reliability of the STAT taxonomy using in-situ simulation resuscitations. METHODS: Two reviewers utilized the STAT taxonomy to score 12 in-situ simulated trauma resuscitations. AEs were reported for each simulation and timestamped in the case of multiple occurrences of a single AE. Inter-rater reliability was assessed using Gwet's AC1. RESULTS: The agreement on all AEs between reviewers was 90.1% (973/1080). The Gwet's AC1 across AE categories were: EMS handover (median 0.72, IQR [0.54, 0.82]), airway and breathing (median 0.91, IQR [0.60, 1.0]), circulation (median 0.91, IQR [0.72, 1.0]), assessment of injuries (median 0.80, IQR [0.24, 0.91]), management of injuries (median 1.00, IQR [1.00, 1.00]), procedure related (median 1.00, IQR [81, 1.00]), patient monitoring and IV access (median 1.00, IQR [1.00, 1.00]), disposition (median 1.00, IQR [1.00, 1.00]), team communication and dynamics (median 0.80, IQR [0.62, 1.00]). CONCLUSIONS: The STAT taxonomy yielded 90.1% agreement and demonstrated excellent inter-rater reliability between reviewers in the in-situ simulation scenario. The STAT taxonomy may serve as a standardized evaluation tool of latent safety threats and adverse events in the trauma bay. Future work should focus on applying this tool to live trauma patients.

Functional Improvement Trajectories After Surgery (FIT After Surgery) study: protocol for a multicentre prospective cohort study to evaluate significant new disability after major surgery in older adults.

INTRODUCTION: Older adults prioritise surviving surgery, but also preservation of their functional status and quality of life. Current approaches to measure postoperative recovery, which focus on death, complications and length of hospitalisation, may miss key relevant domains. We propose that postoperative disability is an important patient-centred outcome to measure intermediate-to-long recovery after major surgery in older adults. METHODS AND ANALYSIS: The Functional Improvement Trajectories After Surgery (FIT After Surgery) study is a multicentre cohort study of 2000 older adults (≥65 years) having major non-cardiac surgery. Its objectives are to characterise the incidence, trajectories, risk factors and impact of new significant disability after non-cardiac surgery. Disability is assessed using WHO Disability Assessment Schedule (WHODAS) 2.0 instrument and participants' level-of-care needs. Disability assessments occur before surgery, and at 1, 3, 6, 9 and 12 months after surgery. The primary outcome is significantly worse WHODAS score or death at 6 months after surgery. Secondary outcomes are (1) significantly worse WHODAS score or death at 1 year after surgery, (2) increased care needs or death at 6 months after surgery and (3) increased care needs or death at 1 year after surgery. We will use multivariable logistic regression models to determine the association of preoperative characteristics and surgery type with outcomes, joint modelling to characterise longitudinal time trends in WHODAS scores over 12 months after surgery, and longitudinal latent class mixture models to identify clusters following similar trajectories of disability. ETHICS AND DISSEMINATION: The FIT After Surgery study has received research ethics board approval at all sites. Recruitment began in December 2019 but was placed on hold in March 2020 because of the COVID-19 pandemic. Recruitment was gradually restarted in October 2020, with 1-year follow-up expected to finish in 2023. Publication of the primary results is anticipated to occur in 2024.

Identifying clinical subtypes in sepsis-survivors with different one-year outcomes: a secondary latent class analysis of the FROG-ICU cohort.

BACKGROUND: Late mortality risk in sepsis-survivors persists for years with high readmission rates and low quality of life. The present study seeks to link the clinical sepsis-survivors heterogeneity with distinct biological profiles at ICU discharge and late adverse events using an unsupervised analysis. METHODS: In the original FROG-ICU prospective, observational, multicenter study, intensive care unit (ICU) patients with sepsis on admission (Sepsis-3) were identified (N = 655). Among them, 467 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct sepsis-survivors clinical classes using readily available data at ICU discharge. The primary endpoint was one-year mortality after ICU discharge. RESULTS: At ICU discharge, two distinct subtypes were identified (A and B) using 15 readily available clinical and biological variables. Patients assigned to subtype B (48% of the studied population) had more impaired cardiovascular and kidney functions, hematological disorders and inflammation at ICU discharge than subtype A. Sepsis-survivors in subtype B had significantly higher one-year mortality compared to subtype A (respectively, 34% vs 16%, p < 0.001). When adjusted for standard long-term risk factors (e.g., age, comorbidities, severity of illness, renal function and duration of ICU stay), subtype B was independently associated with increased one-year mortality (adjusted hazard ratio (HR) = 1.74 (95% CI 1.16-2.60); p = 0.006). CONCLUSIONS: A subtype with sustained organ failure and inflammation at ICU discharge can be identified from routine clinical and laboratory data and is independently associated with poor long-term outcome in sepsis-survivors. Trial registration NCT01367093; https://clinicaltrials.gov/ct2/show/NCT01367093 .

Effect of Time to Treatment With Antiarrhythmic Drugs on Return of Spontaneous Circulation in Shock-Refractory Out-of-Hospital Cardiac Arrest.

Background The effects of amiodarone and lidocaine on the return of spontaneous circulation (ROSC) in relation to time to treatment in patients with out-of-hospital cardiac arrest is not known. We conducted a post hoc analysis of the ROC ALPS (Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo) randomized controlled trial examining the association of time to treatment (drug or placebo) with ROSC at hospital arrival. Methods and Results In the trial, adults with nontraumatic out-of-hospital cardiac arrest with initial refractory ventricular fibrillation or pulseless ventricular tachycardia after at least 1 defibrillation were randomly assigned to receive amiodarone, lidocaine, or placebo. We used logistic regression to examine the association of time to treatment (911 call to study drug administration) with ROSC. An interaction term between treatment and time to treatment was included to determine the potential effect of time on treatment effects. Overall, 1112 (36.7%) patients had ROSC at hospital arrival (350 in the amiodarone arm, 396 in the lidocaine arm, and 366 in the placebo arm). The proportion of patients who had ROSC decreased as time to drug administration increased, in patients treated with amiodarone (odds ratio, 0.92; 95% CI, 0.90-0.94 per minute increase), lidocaine (odds ratio, 0.95; 95% CI, 0.93-0.96), and placebo (odds ratio, 0.95; 95% CI, 0.93-0.96). With shorter times to drug administration, the proportion with ROSC was higher in amiodarone versus placebo recipients. Conclusions The probability of ROSC decreased as time to drug administration increased. The effect of amiodarone but not lidocaine to restore ROSC declined with longer times to drug administration, potentially attributable to its adverse hemodynamic effects.

Children's screen use and school readiness at 4-6 years: prospective cohort study.

BACKGROUND: The primary aim of this study was to determine if screen use in early childhood is associated with overall vulnerability in school readiness at ages 4 to 6 years, as measured by the Early Development Instrument (EDI). Secondary aims were to: (1) determine if screen use was associated with individual EDI domains scores, and (2) examine the association between screen use and EDI domains scores among a subgroup of high screen users. METHODS: This prospective cohort study was carried out using data from young children participating in a large primary care practice-based research network in Canada. Logistic regression analyses were run to investigate the association between screen use and overall vulnerability in school readiness. Separate linear regression models examined the relationships between children's daily screen use and each separate continuous EDI domain. RESULTS: A total of 876 Canadian participants participated in this study. Adjusted logistic regression revealed an association between increased screen use and increased vulnerability in school readiness (p = 0.05). Results from adjusted linear regression demonstrated an association between higher screen use and reduced language and cognitive development domain scores (p = 0.004). Among high screen users, adjusted linear regression models revealed associations between increased screen use and reduced language and cognitive development (p = 0.004) and communication skills and general knowledge domain scores (p = 0.042). CONCLUSIONS: Screen use in early childhood is associated with increased vulnerability in developmental readiness for school, with increased risk for poorer language and cognitive development in kindergarten, especially among high users.

Association Between Physical Activity, Screen Time and Sleep, and School Readiness in Canadian Children Aged 4 to 6 Years.

OBJECTIVE: School readiness is strongly associated with a child's future school success and well-being. The primary objective of this study was to determine whether meeting 24-hour movement guidelines (national physical activity, sedentary behaviors, and sleep recommendations) was associated with school readiness measured with mean scores in each of the 5 developmental domains of the Early Development Instrument (EDI) in Canadian children aged 4 to 6 years. Secondary objectives include examining the following: (1) the association between meeting 24-hour movement guidelines and overall vulnerability in school readiness and (2) the association between meeting individual physical activity, screen use and sleep recommendations, and overall school readiness. METHODS: A prospective cohort study was performed using data from children (aged 4-6 years) who participated in a large-scale primary care practice-based research network. RESULTS: Of the 739 participants (aged 5.9 + 0.12 years) in this prospective cohort study, 18.2% met the 24-Hour Movement Guidelines. Linear regression models (adjusted for child/family demographic characteristics, number of siblings, immigration status, and annual household income) revealed no evidence of an association between meeting all 24-hour movement guidelines and any of the 5 domains of the EDI (p > 0.05). Adjusted linear regression models revealed evidence of an association between meeting screen use guidelines and the "language and cognitive development" (ß = 0.16, p = 0.004) domain, and for the sleep guideline, there was a statistically significant association with the "physical health and well-being" (ß = 0.23, p = 0.001), the "language and cognitive development" (ß = 0.10, p = 0.003), and the "communication skills and general knowledge" (ß = 0.18, p < 0.001) domain. CONCLUSION: Early lifestyle interventions targeting screen use and sleep may be beneficial for improving a child's readiness for school.