Ceragenin-coated endotracheal tubes for the reduction of ventilator-associated pneumonia: a prospective, longitudinal, cross-over, interrupted time, implementation study protocol (CEASE VAP study).

BACKGROUND: Critically ill patients are at high risk of acquiring ventilator-associated pneumonia (VAP), which occurs in approximately 20% of mechanically ventilated patients. VAP results either from aspiration of pathogen-contaminated oropharyngeal secretions or contaminated biofilms that form on endotracheal tubes (ETTs) after intubation. VAP results in increased duration of mechanical ventilation, increased intensive care unit and hospital length of stay, increased risk of death and increased healthcare costs. Because of its impact on patient outcomes and the healthcare system, VAP is regarded as an important patient safety issue and there is an urgent need for better evidence on the efficacy of prevention strategies. Modified ETTs that reduce aspiration of oropharyngeal secretions with subglottic secretion drainage or reduce the occurrence of biofilm with a coating of ceragenins (CSAs) are available for clinical use in Canada. In this implementation study, we will evaluate the efficacy of these two types of Health Canada-licensed ETTs on the occurrence of VAP, and impact on patient-centred outcomes. METHODS: In this ongoing, pragmatic, prospective, longitudinal, interrupted time, cross-over implementation study, we will compare the efficacy of a CSA-coated ETT (CeraShield N8 Pharma) with an ETT with subglottic secretion drainage (Taper Guard, Covidien). The study periods consist of four alternating time periods of 11 or 12 weeks or a total of 23 weeks for each ETT. All patients intubated with the study ETT in each time period will be included in an intention-to-treat analysis. Outcomes will include VAP incidence, mortality and health services utilisation including antibiotic use and length of stay. ETHICS AND DISSEMINATION: This study has been approved by the Health Sciences Research Ethics Board at Queen's University. The results of this study will be actively disseminated through manuscript publication and conference presentations. TRIAL REGISTRATION NUMBER: NCT05761613.

A longitudinal seroepidemiology study to evaluate antibody response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Canada from July 2020 to April 2022: Alberta COVID-19 Childhood Cohort (AB3C) Study.

BACKGROUND: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. This study aimed to estimate the serologic response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Alberta over a two-year period. METHODS: Children with or without prior SARS-CoV-2 infections, were enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records. RESULTS: 1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrolment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% of all infected children after more than 200 days post diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated infected children after more than 200 days post diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children. CONCLUSIONS: In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children, but just over one-half of unvaccinated children, had SARS-CoV-2 spike antibodies indicating infection and/or vaccination, highlighting the benefit of vaccination. It is not yet known whether a high proportion of seropositivity at the present time predicts sustained population-level protection against future SARS-CoV-2 transmission, infection or severe COVID-19 outcomes in children.

Risk factors for postpartum maternal mortality and hospital readmission in low- and middle-income countries: a systematic review.

BACKGROUND: In low- and middle-income countries, approximately two thirds of maternal deaths occur in the postpartum period. Yet, care for women beyond 24 h after discharge is limited. The objective of this systematic review is to summarize current evidence on socio-demographic and clinical risk factors for (1) postpartum mortality and (2) postpartum hospital readmission. METHODS: A combination of keywords and subject headings (i.e. MeSH terms) for postpartum maternal mortality or readmission were searched. Articles published up to January 9, 2021 were identified in MEDLINE, EMBASE, and CINAHL databases, without language restrictions. Studies reporting socio-demographic or clinical risk factors for postpartum mortality or readmission within six weeks of delivery among women who delivered a livebirth in a low- or middle-income country were included. Data were extracted independently by two reviewers based on study characteristics, population, and outcomes. Included studies were assessed for quality and risk of bias using the Downs and Black checklist for ratings of randomized and non-randomized studies. RESULTS: Of 8783 abstracts screened, seven studies were included (total N = 387,786). Risk factors for postpartum mortality included Caesarean mode of delivery, nulliparity, low or very low birthweight, and shock upon admission. Risk factors for postpartum readmission included Caesarean mode of delivery, HIV positive serostatus, and abnormal body temperature. CONCLUSIONS: Few studies reported individual socio-demographic or clinical risk factors for mortality or readmission after delivery in low- and middle-income countries; only Caesarean delivery was consistently reported. Further research is needed to identify factors that put women at greatest risk of post-discharge complications and mortality. Understanding post-discharge risk would facilitate targeted postpartum care and reduce adverse outcomes in women after delivery. TRIAL REGISTRATION: PROSPERO registration number: CRD42018103955.

Medial orbitofrontal cortical regulation of different aspects of Pavlovian and instrumental reward seeking.

RATIONALE: The medial subregion of the orbitofrontal cortex (mOFC) is thought to play an important role representing the expected outcome of a given course of action, as lesioning or inactivating this cortical region results in the adoption of choice strategies based more on observable (rather than previously learned) information. Despite this, its role in mediating basic associative learning remains to be fully clarified. OBJECTIVE: The present series of experiments examined the role of the mOFC in (1) Pavlovian conditioned approach, (2) conditioned reinforcement, (3) extinction, and (4) cue-induced reinstatement of food-seeking behavior. METHODS: Separate cohorts of rats went through Pavlovian or instrumental training. Intra-mOFC infusions of either saline or GABA agonists (to temporarily inactivate neural activity) were given prior to Pavlovian approach, conditioned reinforcement, first or second day of instrumental extinction training, or cue-induced reinstatement test days. RESULTS: mOFC inactivation increased lever-CS contacts in Pavlovian conditioned approach and (2) had no effect on conditioned reinforcement. These manipulations (3) accelerated within-session instrumental extinction during the initial extinction session, but impaired subsequent extinction learning on drug-free days. (4) mOFC inactivation induced differential effects on reinstatement that depended on baseline performance. mOFC inactivation abolished reinstatement in "Reinstater" rats (who displayed robust responding under control conditions) and robustly increased reinstatement in "Non-Reinstater" rats (who showed little reinstatement under control conditions) suggesting that individual differences in reinstatement may be supported by differences in mOFC mediated representations of expected outcomes. CONCLUSIONS: These findings have important implications for understanding how the mOFC uses stimulus-outcome and action-outcome expectancies to guide behavior, and how dysfunction within this region may contribute to pathological patterns of reward seeking.

Effectiveness of hospital avoidance interventions among elderly patients: A systematic review.

OBJECTIVE: Older patients with complex care needs and limited personal and social resources are heavy users of emergency department (ED) services and are often admitted when they present to the ED. Updated information is needed regarding the most effective strategies to appropriately avoid ED presentation and hospital admission among older patients. METHODS: This systematic review aimed to identify interventions that have demonstrated effectiveness in decreasing ED use and hospital admissions in older patients. We conducted a comprehensive literature search within Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials from database inception to July 2019 with no language restrictions. Interventional study designs conducted in populations of 65 years and older were included. Primary outcomes were ED visits and hospital admissions. Secondary outcomes included hospital readmission, mortality, cost, and patient-reported outcomes. RESULTS: Of 7,943 citations reviewed for eligibility, 53 studies were included in our qualitative synthesis, including 26 randomized controlled trials (RCT), 8 cluster-RCTs, and 19 controlled before-after studies. Data characterization revealed that community-based strategies reduced ED visits, particularly those that included comprehensive geriatric assessments and home visits. These strategies reported decreases in mean ED use (for interventions versus controls) ranging from -0.12 to -1.32 visits/patient. Interventions that included home visits also showed reductions in hospital admissions ranging from -6% to -14%. There was, however, considerable variability across individual studies with respect to outcome reporting, statistical analyses, and risk of bias, which limited our ability to further quantify the effect of these interventions. CONCLUSION: Various interventional strategies to avoid ED presentations and hospital admissions for older patients have been studied. While models of care that include comprehensive geriatric assessments and home visits may reduce acute care utilization, the standardization of outcome measures is needed to further delineate which parts of these complex interventions are contributing to efficacy. The potential effects of multidisciplinary team composition on patient outcomes also warrant further investigation.

Identification of validated case definitions for medical conditions used in primary care electronic medical record databases: a systematic review.

Objectives: Data derived from primary care electronic medical records (EMRs) are being used for research and surveillance. Case definitions are required to identify patients with specific conditions in EMR data with a degree of accuracy. The purpose of this study is to identify and provide a summary of case definitions that have been validated in primary care EMR data. Materials and Methods: We searched MEDLINE and Embase (from inception to June 2016) to identify studies that describe case definitions for clinical conditions in EMR data and report on the performance metrics of these definitions. Results: We identified 40 studies reporting on case definitions for 47 unique clinical conditions. The studies used combinations of International Classification of Disease version 9 (ICD-9) codes, Read codes, laboratory values, and medications in their algorithms. The most common validation metric reported was positive predictive value, with inconsistent reporting of sensitivity and specificity. Discussion: This review describes validated case definitions derived in primary care EMR data, which can be used to understand disease patterns and prevalence among primary care populations. Limitations include incomplete reporting of performance metrics and uncertainty regarding performance of case definitions across different EMR databases and countries. Conclusion: Our review found a significant number of validated case definitions with good performance for use in primary care EMR data. These could be applied to other EMR databases in similar contexts and may enable better disease surveillance when using clinical EMR data. Consistent reporting across validation studies using EMR data would facilitate comparison across studies. Systematic review registration: PROSPERO CRD42016040020 (submitted June 8, 2016, and last revised June 14, 2016).

Identification of validated case definitions for chronic disease using electronic medical records: a systematic review protocol.

BACKGROUND: Primary care electronic medical record (EMR) data are being used for research, surveillance, and clinical monitoring. To broaden the reach and usability of EMR data, case definitions must be specified to identify and characterize important chronic conditions. The purpose of this study is to identify all case definitions for a set of chronic conditions that have been tested and validated in primary care EMR and EMR-linked data. This work will provide a reference list of case definitions, together with their performance metrics, and will identify gaps where new case definitions are needed. METHODS: We will consider a set of 40 chronic conditions, previously identified as potentially important for surveillance in a review of multimorbidity measures. We will perform a systematic search of the published literature to identify studies that describe case definitions for clinical conditions in EMR data and report the performance of these definitions. We will stratify our search by studies that use EMR data alone and those that use EMR-linked data. We will compare the performance of different definitions for the same conditions and explore the influence of data source, jurisdiction, and patient population. DISCUSSION: EMR data from primary care providers can be compiled and used for benefit by the healthcare system. Not only does this work have the potential to further develop disease surveillance and health knowledge, EMR surveillance systems can provide rapid feedback to participating physicians regarding their patients. Existing case definitions will serve as a starting point for the development and validation of new case definitions and will enable better surveillance, research, and practice feedback based on detailed clinical EMR data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016040020.