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The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use.

Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data. The objective of this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials. This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered 'non-adherent to the protocol' but for whom data are available, and participants with missing data. Systematic reviewer authors should include data from 'non-adherent' participants excluded from the primary study authors' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events. This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results.

In this trial, high-frequency oscillatory ventilation was compared with conventional ventilation with a lung-protective protocol. When the study was stopped early, hospital mortality was 47% with HFOV versus 35% with the control ventilation strategy. The acute respiratory distress syndrome (ARDS) is a common complication of critical illness. 1 , 2 Mortality is high, and survivors often have long-term complications. 3 , 4 Although mechanical ventilation is life-sustaining for patients with ARDS, it can perpetuate lung injury. Basic research suggests that repetitive overstretching or collapse of lung units with each respiratory cycle can generate local and systemic inflammation, contributing to multiorgan failure and death. 5 Consistent with these findings are data from clinical trials that support the use of smaller tidal volumes (6 vs. 12 ml per kilogram of predicted body weight) 6 and higher levels of positive end-expiratory pressure (PEEP). . . .

Death is universal, yet relatively little is known about how Canadians experience their death. Using novel decedent interview data from the Canadian Longitudinal Study on Aging we describe the prevalence and characteristics of peace with dying among older Canadians. We conducted a secondary analysis of decedent interview data from the Canadian Longitudinal Study on Aging. Proxies of deceased Canadian Longitudinal Study on Aging participants reported on participants' end-of-life experiences between January 2012 to March 2022. We examined end-of-life characteristics and their association with proxy reports of experiencing peace with dying. We conducted regression analysis to explore the association between demographic and end-of-life characteristics and experiencing peace with dying. Of 3,672 deceased participants, 1,287 (35.0%) had a completed decedent questionnaire and were included in the analysis. Respondents reported that two-thirds (66.0%) of the deceased experienced peace with dying and 17% did not experience peace with dying. The unadjusted odds of experiencing peace with dying were higher for those with an appointed power of attorney (OR 1.80; CI 1.39-2.33), those who died of cancer (OR 1.71; CI 1.27-2.30), those in hospice/receiving palliative care (OR 1.67; CI 1.19-2.37), individuals older than 75 years (OR 1.55; CI 1.04-2.30), or widowed (OR 1.53; CI 1.12-2.10). Widowhood (OR 1.51; CI 1.01-2.29), having an end-of-life SDM (OR 1.58; CI 1.14-2.17), and dying of cancer (OR 1.67; CI 1.19-2.23) increased the adjusted odds of dying with peace. Close to 1 in 5 older Canadians may not experience peace with dying, which supports greater focus on improving the end-of-life care. Our findings suggest that advanced planning may enhance the experience of a peaceful death in Canada.

AbstractObjectiveTo analyse the association between survival from critical illness and suicide or self-harm after hospital discharge.DesignPopulation based cohort study using linked and validated provincial databases.SettingOntario, Canada between January 2009 and December 2017 (inclusive).ParticipantsConsecutive adult intensive care unit (ICU) survivors (≥18 years) were included. Linked administrative databases were used to compare ICU hospital survivors with hospital survivors who never required ICU admission (non-ICU hospital survivors). Patients were categorised based on their index hospital admission (ICU or non-ICU) during the study period.Main outcome measuresThe primary outcome was the composite of death by suicide (as noted in provincial death records) and deliberate self-harm events after discharge. Each outcome was also assessed independently. Incidence of suicide was evaluated while accounting for competing risk of death from other causes. Analyses were conducted by using overlap propensity score weighted, cause specific Cox proportional hazard models.Results423 060 consecutive ICU survivors (mean age 61.7 years, 39% women) were identified. During the study period, the crude incidence (per 100 000 person years) of suicide, self-harm, and the composite of suicide or self-harm among ICU survivors was 41.4, 327.9, and 361.0, respectively, compared with 16.8, 177.3, and 191.6 in non-ICU hospital survivors. Analysis using weighted models showed that ICU survivors (v non-ICU hospital survivors) had a higher risk of suicide (adjusted hazards ratio 1.22, 95% confidence interval 1.11 to 1.33) and self-harm (1.15, 1.12 to 1.19). Among ICU survivors, several factors were associated with suicide or self-harm: previous depression or anxiety (5.69, 5.38 to 6.02), previous post-traumatic stress disorder (1.87, 1.64 to 2.13), invasive mechanical ventilation (1.45, 1.38 to 1.54), and renal replacement therapy (1.35, 1.17 to 1.56).ConclusionsSurvivors of critical illness have increased risk of suicide and self-harm, and these outcomes were associated with pre-existing psychiatric illness and receipt of invasive life support. Knowledge of these prognostic factors might allow for earlier intervention to potentially reduce this important public health problem.

To describe pre-ICU frailty in critically ill patients using the Clinical Frailty Scale (CFS). We included patients ≥18years admitted to 2 ICUs in Hamilton, Canada. The ICU Research Coordinator (RC) generated 3 CFS scores using: 1) chart review, 2) family interview, 3) patient interview. Subsequently, an overall impression was captured in a final score. Mean differences were calculated to assess the RC intra-rater reliability and inter-rater reliability of chart reviews by the RC, Occupational Therapist (OT), and Geriatrics Resident (GR). Scores were also compared between younger and older patients. We also analyzed the relationship between CFS scores and mortality. We prospectively enrolled 150 patients (mean age 63.8 [SD 15.3] years, APACHE II score 21 [SD 7.3]). CFS were similar between RC, OT, and GR chart reviews (p>0.05 for all comparisons). There was no difference between RC chart review and RC final score, or between RC patient interview and RC final score. Scores following the RC family interview and the RC final score were significantly different (−0.24, 95% CI −0.38, −0.09, p<0.01). Each 1-point increase in the final CFS scored by the RC was weakly associated with ICU mortality (odds ratio 1.18, 95% CI 0.84–1.66, p=0.33), and hospital mortality (OR 1.19, 95% CI 0.89, −1.59, p=0.24). CFS scores can be generated using medical chart review and can be reliably completed by ICU clinicians and research staff. •Using the Clinical Frailty Scale is feasible in the ICU.•Frailty scores are similar across ages despite higher illness severity in older patients.•Chart review and interviews yield similar frailty scores.

Previous trials of higher positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) failed to demonstrate mortality benefit, possibly because of differences in lung recruitability among patients with ARDS. To determine whether the physiological response to increased PEEP is associated with mortality. In a secondary analysis of the Lung Open Ventilation Study (LOVS, n = 983), we examined the relationship between the initial response to changes in PEEP after randomization and mortality. We sought to corroborate our findings using data from a different trial of higher PEEP (ExPress, n = 749). The oxygenation response (change in ratio of arterial partial pressure of oxygen to fraction of inspired oxygen: P/F) after the initial change in PEEP after randomization varied widely (median, 9.5 mm Hg; interquartile range, -16 to 47) and was only weakly related to baseline P/F or the magnitude of PEEP change. Among patients in whom PEEP was increased after randomization, an increase in P/F was associated with reduced mortality (multivariable logistic regression; adjusted odds ratio, 0.80 [95% confidence interval, 0.72-0.89] per 25-mm Hg increase in P/F), particularly in patients with severe disease (baseline P/F [less-than-or-equal-to] 150 mm Hg). Changes in compliance and dead space were not associated with mortality. These findings were confirmed by a similar analysis of data from the ExPress trial. Patients with ARDS who respond to increased PEEP by improved oxygenation have a lower risk of death. The oxygenation response to PEEP might be used to predict whether patients will benefit from higher versus lower PEEP.

Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study. We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level ≤ 6.1 mmol/L v. ≤ 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU. Une version française de ce résumé est disponible à l'adresse www.cmaj.ca/cgi/content/full/180/8/821/DC1 CMAJ 2009;180(8):821-7

PurposeGuidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.MethodsWe searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.ResultsIncluded trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).ConclusionsTargeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

Only a small proportion of COVID-19 patients in Canada have been recruited into clinical research studies. One reason is that few community intensive care units (ICUs) in Canada participate in research. The objective of this study was to examine the motivating factors, barriers and facilitators to research participation amongst Canadian community ICU stakeholders. A cross-sectional online survey was distributed between May and November 2020. The survey focused on 6 domains: participant demographics, ICU characteristics, ICU research infrastructure, motivating factors, perceived barriers, and perceived facilitators. Responses were received from 73 community ICU stakeholders, representing 18 ICUs. 7/18 ICUs had a clinical research program. Participants rated their interest in pandemic research at a mean of 5.2 (Standard Deviation [SD] = 1.9) on a 7-point Likert scale from ‘not interested’ to ‘very interested’. The strongest motivating factor for research participation was the belief that research improves clinical care and outcomes. The most significant facilitators of research involvement were the availability of an experienced research coordinator and dedicated external funding to cover start-up costs, while the most significant barriers to research involvement were a lack of start-up funding for a research coordinator and a lack of ICU research experience. Canadian Community ICU stakeholders are interested in participating in pandemic research but lack basic infrastructure, research personnel, research experience and start-up funding. Evolution of a research support model at community hospitals, where most patients receive acute care, may increase research participation and improve the generalizability of funded research in Canada.