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Among atrial fibrillation (AF) patients, it is unclear whether the efficacy and safety of direct oral anticoagulants (DOAC) relative to warfarin is consistent across various levels of international normalized ratio (INR) control. To determine the efficacy and safety of DOAC agents compared with warfarin for patients with various levels of anticoagulation control as reflected by their time in therapeutic range (TTR), we conducted a systematic review and meta-analysis of published randomized controlled trials of DOAC versus (vs) warfarin which reported outcomes stratified by TTR. Based on reported center-based TTR (cTTR) ranges, degrees of INR control were categorized into 3 cTTR strata: low (60%), intermediate (60% to 66%), and high (66%). Pooled hazard ratios (HR) and 95% confidence intervals (CI) were determined for stroke or systemic embolism (SSE), major bleeding, and intracranial hemorrhage (ICH). Across all cTTR strata, DOAC-treated patients had lower risk of SSE versus warfarin, with a HR of 0.73 (95% CI 0.61 to 0.88) for the low, 0.76 (95% CI 0.59 to 0.98) intermediate; and 0.78 (95% CI 0.63 to 0.96) high cTTR subgroups. Compared with warfarin, DOAC-treated patients had lower risk of major bleeding in the low and intermediate cTTR strata, and similar risk in the highest cTTR stratum (HR 1.00, 95% CI 0.80 to 1.26). Patients treated with DOAC had lower risk of ICH compared with warfarin (HR 0.55, 95% CI; 0.40 to 0.74) which was observed across all cTTR strata. In conclusion, regardless of the degree of INR control, DOAC agents are preferable over warfarin as stroke prevention therapy for patients with AF.

This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.

Background The optimal donor heart preservation and management strategy during heart transplantation remains controversial. We report the results of a systematic review and meta-analysis of the effect of supplemental cardioplegia administration during donor heart implant for transplantation. Methods We searched MEDLINE and Embase databases until February 2019 for studies comparing patients who received transplants with the donor heart given supplemental cardioplegia or not. Data were extracted by 2 independent investigators. The main outcomes were early morbidity and mortality. Results Included were 7 retrospective observational studies (4 comparing to historical controls) and 3 randomized controlled trials enrolling 1125 patients. Supplemental cardioplegia included crystalloid and blood cardioplegia given continuous retrograde or as terminal "hot shots." Supplemental cardioplegia was associated with improved early mortality (risk ratio [RR], 0.55; 95% confidence interval [CI], 0.35-0.87; P Conclusions Administration of supplemental cardioplegia may be associated with a reduction in organ ischemic injury and shorter intensive care stay as well as improvement in early survival after transplantation. This strategy may be a simple and cost-effective adjunct to improve outcomes of heart transplantation, especially in an era of increasing use of marginal donor organs. Further investigation will be needed to confirm the findings of this hypothesis-generating study.

Aortic valve-sparing operations theoretically have fewer stroke and bleeding complications but may increase late reoperation risk versus composite valve grafts.We meta-analyzed all studies comparing aortic valve-sparing (reimplantation and remodelling) and composite valve-grafting (bioprosthetic and mechanical) procedures. Early outcomes were all-cause mortality, reoperation for bleeding, myocardial infarction, and thromboembolism/stroke. Long-term outcomes included all-cause mortality, reintervention, bleeding, and thromboembolism/stroke. Studies exclusively investigating dissection or pediatric populations were excluded.A total of 3794 patients who underwent composite valve grafting and 2424 who underwent aortic valve-sparing procedures were included from 9 adjusted and 17 unadjusted observational studies. Mean follow-up was 5.8 ± 3.0 years. Aortic valve sparing was not associated with any difference in early mortality, bleeding, myocardial infarction, or thromboembolic complications. Late mortality was significantly lower after valve sparing (incident risk ratio, 0.68; 95% confidence interval [CI], 0.54-0.87; P.01). Late thromboembolism/stroke (incident rate ratio, 0.36; 95% CI, 0.22-0.60; P.01) and bleeding (incident rate ratio, 0.21; 95% CI, 0.11-0.42; P .01) risks were lower after valve sparing. Procedure type did not affect late reintervention.Aortic valve sparing appears to be safe and associated with reduced late mortality, thromboembolism/stroke, and bleeding compared with composite valve grafting. Late durability is equivalent. Aortic valve sparing should be considered in patients with favorable aortic valve morphology.

Purpose Severe acute kidney injury (AKI) is associated with a significant risk of mortality and persistent renal replacement therapy (RRT) dependence. The objective of this study was to develop prediction models for mortality at 90-day and 1-year following RRT initiation in critically ill patients with AKI. Methods All patients who commenced RRT in the intensive care unit for AKI at a tertiary care hospital between 2007 and 2014 constituted the development cohort. We evaluated the external validity of our mortality models using data from the multicentre OPTIMAL-AKI study. Results The development cohort consisted of 594 patients, of whom 320(54%) died and 40 (15% of surviving patients) remained RRT-dependent at 90-day Eleven variables were included in the model to predict 90-day mortality (AUC:0.79, 95%CI:0.76–0.82). The performance of the 90-day mortality model declined upon validation in the OPTIMAL-AKI cohort (AUC:0.61, 95%CI:0.54–0.69) and showed modest calibration. Similar results were obtained for mortality model at 1-year. Conclusions Routinely collected variables at the time of RRT initiation have limited ability to predict mortality in critically ill patients with AKI who commence RRT.

BACKGROUND The optimal mitral prosthesis in young patients is unclear. This systematic review and meta-analysis were performed to compare outcomes between bileaflet mechanical mitral valve replacement (mMVR) and bioprosthesis mitral valve replacement (bioMVR) for MVR patients aged less than 70 years. METHODS We searched MEDLINE and EMBASE databases from inception to July 2018 for studies comparing surgical outcomes of mMVR vs bioMVR. RESULTS There were 14 observational studies with 20 219 patients (n = 14 658 mMVR and n = 5561 bioMVR). Patients receiving an mMVR were younger with fewer comorbidities including renal failure, dialysis, and less-infective endocarditis (P

Objectives We sought to evaluate the impact of transitions of care among staff intensivists on the compliance with evidence-based processes of care. Design Cohort study using data from the Toronto Intensive Care Observational Registry. Setting Seven academic ICUs in Toronto, Ontario. Patients Critically ill mechanically ventilated adult patients. Interventions We explored the effects of the weekly transition of care among staff intensivists on compliance with three evidence-based processes of care (spontaneous breathing trials, lung-protective ventilation, and neuromuscular blocking agents). Two practices that are less guided by evidence (early discontinuation of antibiotics and extubation attempts) served as positive controls. We conducted the analysis using generalized estimating equations to account for clustering at the patient level. Measurements and main results The cohort consisted of 10,570 patients admitted between June 2014 and August 2018. Compliance varied for each practice (63.6%, 42.5%, and 21.1% for lung-protective ventilation, spontaneous breathing trials, and neuromuscular blockade, respectively). There was no effect of transitions of care on compliance with spontaneous breathing trials (odds ratio, 1.00; 95% CI, 0.95-1.07), lung-protective ventilation (odds ratio, 1.07, 95% CI, 0.90-1.26), or neuromuscular blockade use (odds ratio, 0.95; 95% CI, 0.75-1.20). However, early antibiotic discontinuation was more likely (odds ratio, 1.23; 95% CI, 1.06-1.42) and extubation attempts were less frequent (odds ratio, 0.77; 95% CI, 0.65-0.93) after a transition of care. Conclusions We observed no significant impact of transitions of care between individual staff physicians on evidence-based processes of care for mechanically ventilated adult patients. However, transitions were associated with a lower likelihood of extubation and higher odds of earlier discontinuation of antibiotics.

BACKGROUND Mitral valve (MV) disease with mitral annular calcification (MAC) poses a surgical challenge and the clinical outcomes of MV surgery as well as transcatheter mitral valve replacement (TMVR) remain relatively unexplored. We performed a systematic review and meta-analysis to assess the effects of MAC on clinical outcomes following MV surgery and TMVR. METHODS We searched MEDLINE and EMBASE databases until February 2019 for studies comparing clinical outcomes of MV surgery or TMVR in patients with and without MAC. Data were extracted by two independent investigators. Outcomes were perioperative and midterm complications and mortality. RESULTS Seven observational studies enrolling 2902 patients were included. MAC patients were older, more likely to be female with greater chronic lung disease and kidney failure. Perioperative mortality was similar between patients with and without MAC undergoing MV surgery (risk ratio [RR], 1.15; 95% confidence interval [CI], 0.50-2.65; P = .74). MAC was associated with a higher risk of bleeding, permanent pacemaker implantation, and periprosthetic leak. Midterm mortality was greater in MAC patients undergoing MV surgery (incident rate ratio [IRR], 1.32; 95% CI, 1.05-1.67; P = .02). MAC patients undergoing TMVR had higher perioperative (RR, 4.65; 95% CI, 2.93-7.38; P

BACKGROUND AND AIM OF THE STUDY We compared early and late outcomes of surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS) and pulmonary hypertension (PHT). METHODS We searched MEDLINE and EMBASE databases until July 2018 for studies comparing patients with AS and none, mild-moderate, or severe PHT undergoing SAVR. Random-effects meta-analysis was performed. RESULTS There were 12 observational studies with 70 676 patients with median follow-up 4.0 years (interquartile range, 2.6-4 years). Compared to patients with no PHT, patients with any PHT undergoing SAVR were older (mean difference [MD], 2.31 years; 95% confidence interval [CI], 1.38-3.23 years; P

BackgroundIn patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity.MethodsProspective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering.ResultsSeventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0–50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering.ConclusionLow levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity.Trial RegistrationClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.

Background The burden of frailty on cardiac surgical outcomes is incompletely understood. Here we perform a systematic review and meta-analysis of studies comparing frail versus pre-frail versus non-frail patients following cardiac surgery. Methods We searched MEDLINE and EMBASE databases until July 2018 for studies comparing cardiac surgery outcomes in “frail”, “pre-frail” and “non-frail” patients. Data was extracted in duplicate. Primary outcome was operative mortality. Results There were 19 observational studies with 66,448 patients. Frail patients were more likely female (risk ratio [RR]1.7; 95%CI:1.5–1.9), older (mean difference: 2.4; 95%CI:1.3–3.5 years older) with greater comorbidities and higher STS-PROM. Frailty (RR2.35; 95%CI:1.57–3.51; p p p p = 0.002). Frail (Hazard Ratio [HR]3.27; 95%CI:1.93–5.55; p p = 0.005) had worse mid-term mortality (median follow-up 1 years [range 0.5–4 years]). After adjustment for baseline imbalances, frailty was still associated with greater operative mortality (odds ratio [OR]1.97; 95%CI:1.51–2.57; p p < 0.00001) and midterm mortality (HR1.37; 95%CI:1.03–1.83; p = 0.03). Conclusion In patients undergoing cardiac surgery, frailty and pre-frailty were associated with 2-fold and 1.5-fold greater adjusted operative mortality, respectively, greater adjusted perioperative complications and frailty was associated with almost 5-fold risk of non-home discharge. Graphical abstract Burden of frailty and pre-frailty on cardiac surgical outcomes.

Background Transition from continuous renal replacement therapy (CRRT) to intermittent renal replacement therapy (IRRT) can be associated with intra-dialytic hypotension (IDH) although data to inform the definition of IDH, its incidence and clinical implications, are lacking. We aimed to describe the incidence and factors associated with IDH during the first IRRT session following transition from CRRT and its association with hospital mortality. This was a retrospective single-center cohort study in patients with acute kidney injury for whom at least one CRRT-to-IRRT transition occurred while in intensive care. We assessed associations between multiple candidate definitions of IDH and hospital mortality. We then evaluated the factors associated with IDH. Results We evaluated 231 CRRT-to-IRRT transitions in 213 critically ill patients with AKI. Hospital mortality was 43.7% (n = 93). We defined IDH during the first IRRT session as 1) discontinuation of IRRT for hemodynamic instability; 2) any initiation or increase in vasopressor/inotropic agents or 3) a nadir systolic blood pressure of p Conclusions IDH events during CRRT-to-IRRT transition occurred in nearly half of patients and were independently associated with hospital mortality. We identified several characteristics that anticipate the development of IDH following the initiation of IRRT.

Background Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. Methods This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. Results BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). Conclusions Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders.

Objective The management of concomitant mild-to-moderate aortic stenosis (AS) at the time of coronary artery bypass graft (CABG) is controversial. Here we perform a systematic review and meta-analysis of CABG and aortic valve replacement (AVR) versus CABG alone in patients with mild–moderate AS. Methods We searched MEDLINE and EMBASE databases until July 2018 for studies comparing CABG & AVR versus CABG in patients with mild–moderate AS undergoing coronary bypass. Data were extracted by 2 independent investigators. The main outcomes were operative mortality, long-term survival, and reintervention for AS. Results There were 6 unmatched retrospective observational studies with 1,172 patients (median follow-up 4.7 [interquartile range: 4.3 to 5.3] years). Patients undergoing CABG & AVR had less severe coronary artery disease. There were no differences in operative mortality (relative risk [RR]: 1.07; 95% CI, 0.59 to 1.94; P = 0.8). CABG & AVR was associated with greater incidence of stroke, bleeding, renal failure, and mediastinitis. At median follow-up of 5 years, there was no difference in long-term mortality (incidence rate ratio [IRR]:1.44; 95% CI, 0.83 to 2.51; P = 0.19), but CABG & AVR was associated with 73% lower risk of reoperation for AS ( n = 13/485 versus n = 71/702; IRR: 0.27; 95% CI, 0.14 to 0.51; P < 0.001). Conclusions In patients undergoing CABG with mild–moderate AS, combining AVR with CABG was associated with no difference in operative mortality but with increased risk of stroke, bleeding, renal failure, and mediastinitis. Long-term mortality was not different, but a risk of reoperation for AS at 5 years was 73% lower. Given the increasingly wide availability and safety of transcatheter aortic valve replacement (TAVR), one may consider a conservative approach toward concomitant mild–moderate AS.

Objectives It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context. Design We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients. Setting Ten and 11 ICUs in Canada, respectively. Patients Parallel trials of younger (RELEASE Interventions Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists. Measurements and main results In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined. Conclusions Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

Background and objectives Older patients in the intensive care unit are at greater risk of AKI; however, use of kidney replacement therapy in this population is poorly characterized. We describe the triggers and outcomes associated with kidney replacement therapy in older patients with AKI in the intensive care unit. Design, setting, participants, & measurements Our study was a prospective cohort study in 16 Canadian hospitals from September 2013 to November 2015. Patients were ≥65 years old, were critically ill, and had severe AKI; exclusion criteria were urgent kidney replacement therapy for a toxin and ESKD. We recorded triggers for kidney replacement therapy (primary exposure), reasons for not receiving kidney replacement therapy, 90-day mortality (primary outcome), and kidney recovery. Results Of 499 patients, mean (SD) age was 75 (7) years old, Charlson comorbidity score was 3.0 (2.3), and median (interquartile range) Clinical Frailty Scale score was 4 (3–5). Most were receiving mechanical ventilation (64%; n=319) and vasoactive support (63%; n=314). Clinicians were willing to offer kidney replacement therapy to 361 (72%) patients, and 229 (46%) received kidney replacement therapy. Main triggers for kidney replacement therapy were oligoanuria, fluid overload, and acidemia, whereas main reasons for not receiving therapy were anticipated recovery (67%; n=181) and therapy not consistent with patient preferences for care (24%; n=66). Ninety-day mortality was similar in patients who did and did not receive kidney replacement therapy (50% versus 51%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.58 to 1.06); however, decisions to offer kidney replacement therapy varied significantly by patient mix, acuity, and perceived benefit. There were no differences in health-related quality of life or rehospitalization among survivors. Conclusions Most older, critically ill patients with severe AKI were perceived as candidates for kidney replacement therapy, and approximately one half received therapy. Both willingness to offer kidney replacement therapy and reasons for not starting showed heterogeneity due to a range in patient-specific factors and clinician perceptions of benefit.

OBJECTIVES The surgical management of tricuspid regurgitation (TR) at the time of mitral valve surgery remains controversial. Our objectives were to determine the safety and efficacy of tricuspid valve (TV) repair during mitral valve surgery in a meta-analysis. METHODS MEDLINE and EMBASE were searched from 1946 to 2017 for all studies comparing TV repair to no intervention at the time of mitral valve surgery on early and late mortality and late TR. A random-effects meta-analysis of all outcomes was performed. RESULTS One thousand four hundred and seventeen studies were retrieved and a total of 17 studies [2 randomized clinical trial (n = 211), 11 adjusted observational studies (n = 3848) and 4 unadjusted observational studies (n = 67 010)] that compared TV repair (n = 11 787) to no intervention (n = 56 027) at a mean follow-up of 6.0 ± 0.64 years were included. There was no difference in 30-day/in-hospital mortality between repair and no repair [risk ratio (RR) 1.19, 95% confidence interval (95% CI) 0.70–2.02; P = 0.52]. The incidence of new permanent pacemaker implantation was higher in the TV repair group (RR 2.73, 95% CI 2.57–2.89; P CONCLUSIONS TV repair appears safe in the perioperative period and may reduce future recurrent TR without any survival benefit.

BACKGROUND Antimicrobial stewardship programs have been established in hospitals, but less studied in long‐term care facilities (LTCFs), a setting with unique challenges related to patient populations and available resources. This systematic review sought to provide a comprehensive assessment of antimicrobial stewardship interventions implemented in LTCFs, using meta‐analysis to examine their impact on overall antimicrobial use. METHODS Electronic searches of MEDLINE, Embase, and CINAHL (1990 to July 2018) identified any antimicrobial stewardship interventions in LTCFs, with no restriction on patient population, study design, or outcomes. Intervention components were categorized using the Cochrane Effective Practice and Organization of Care taxonomy on implementation strategies. Random‐effects meta‐analysis used ratio of means to facilitate pooling of different metrics of antimicrobial use. RESULTS Eighteen studies (one randomized controlled trial [RCT], four cluster RCTs, four controlled pre/post studies, and nine uncontrolled pre/post studies) met inclusion, using 13 different antimicrobial stewardship intervention strategies; 15 studies used multifaceted (maximum, seven; median, four) interventions. The three most commonly implemented strategies were educational materials, educational meetings, and guideline implementation. Intervention labor intensity and resource requirements varied considerably among interventions. Meta‐analysis of 11 studies demonstrated that antimicrobial stewardship strategies were associated with a 14% reduction in overall antimicrobial use (95% confidence interval = −8% to −20%; P < .0001), with similar results by study design but high heterogeneity (I2 = 86%) for the uncontrolled pre/post study subgroup and no heterogeneity (I2 = 0%) for the cluster RCT and controlled pre/post study subgroups. Funnel plot analysis suggested publication bias, with a lack of publication of smaller studies showing increased antibiotic use. CONCLUSION Antimicrobial stewardship strategies implemented in long‐term care vary considerably in design and resource intensity, but collectively suggest potential to reduce antimicrobial use in this challenging setting. J Am Geriatr Soc 67:392–399, 2019.

Background The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. Methods We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. Results A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. Conclusions After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

BackgroundIntensive care unit (ICU) patients are at high risk of anemia, and phlebotomy is a potentially modifiable source of blood loss. Our objective was to quantify daily phlebotomy volume for ICU patients, including blood discarded as waste during vascular access, and evaluate the impact of phlebotomy volume on patient outcomes.MethodsThis was a retrospective observational cohort study between September 2014 and August 2015 at a tertiary care academic medical-surgical ICU. A prospective audit of phlebotomy practices in March 2018 was used to estimate blood waste during vascular access. Multivariable logistic regression was used to evaluate phlebotomy volume as a predictor of ICU nadir hemoglobin < 80 g/L, and red blood cell transfusion.ResultsThere were 428 index ICU admissions, median age 64.4 yr, 41% female. Forty-four patients (10%) with major bleeding events were excluded. Mean bedside waste per blood draw (144 draws) was: 3.9 mL from arterial lines, 5.5 mL central venous lines, and 6.3 mL from peripherally inserted central catheters. Mean phlebotomy volume per patient day was 48.1 ± 22.2 mL; 33.1 ± 15.0 mL received by the lab and 15.0 ± 8.1 mL discarded as bedside waste. Multivariable regression, including age, sex, admission hemoglobin, sequential organ failure assessment score, and ICU length of stay, showed total daily phlebotomy volume was predictive of hemoglobin ConclusionA substantial portion of daily ICU phlebotomy is waste discarded during vascular access. Average ICU phlebotomy volume is independently associated with ICU acquired anemia and red blood cell transfusion which supports the need for phlebotomy stewardship programs.

Background Sustained low efficiency dialysis (SLED) has emerged as an alternative to continuous renal replacement therapy (CRRT) for the treatment of acute kidney injury (AKI) in critically ill patients. However, there is limited information on the short- and long-term outcomes of SLED compared to CRRT. Methods We conducted a retrospective cohort study of patients with AKI who commenced either SLED or CRRT in ICUs at a tertiary care hospital in Toronto, Canada. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at one year, and dialysis dependence at 90 days and one year. All outcomes were ascertained by linkage to provincial datasets. Results We identified 284 patients, of whom 95 and 189 commenced SLED and CRRT, respectively. Compared to SLED recipients, more CRRT recipients were mechanically ventilated (96% vs 86%, p = 0.002) and receiving vasopressors (94% vs 84%, p = 0.01) at the time of RRT initiation. At 90 days following RRT initiation, 52 (55%) and 126 (67%) SLED and CRRT recipients, respectively, died (adjusted risk ratio (RR) 0.91, 95% CI 0.75–1.11). There was no inter-modality difference in time to death through 90 days (adjusted hazard ratio 0.90, 95% CI 0.64–1.27). Among patients surviving to Day 90, a higher proportion of SLED recipients remained RRT dependent (10 (23%) vs 6 (10%) CRRT recipients, adjusted RR 2.82, 95% CI 1.02–7.81). At one year, there was no difference in mortality or dialysis dependence. Conclusions Among critically ill patients with acute kidney injury, mortality at 90 days and one year was not different among patients initiating SLED as compared to CRRT.

Background Most intensive care patients require substitute decision makers (SDMs) to make decisions. The SDMs may prefer an active, shared, or passive decision-making role. Role incongruence is when preferred and actual roles differ. Objective To evaluate the impact of decision-making role preferences and role incongruence on psychological distress symptoms in SDMs. Methods A multicenter, interviewer-administered survey was conducted among SDMs of critically ill adults. The Control Preferences Scale was used to evaluate role preferences. Psychological distress was defined as anxiety, depression, or posttraumatic stress symptoms with predefined cut points on the Hospital Anxiety and Depression Scale (score > 10 on the anxiety or the depression subscale) and Impact of Events Scale (score > 30). Results One hundred eighty SDMs were recruited; 64% responded. Most were white (71%) and female (65%); 46% were spouses. Role preferences varied: active, 24%; shared, 44%; and passive, 31%. Almost half (49%) reported incongruence. Symptom prevalence was 50% for posttraumatic stress, 32% for anxiety, and 16% for depression. Most (56%) reported some psychological distress. In multivariable logistic regression, the composite outcome of psychological distress was independently associated with patient death (odds ratio, 2.95; 95% CI, 1.08-8.02; P = .03), female sex of SDM (odds ratio, 2.96; 95% CI, 1.49-5.89; P = .002), and incongruence (odds ratio, 3.26; 95% CI, 1.67-6.36; P < .001). Conclusions Adverse psychological symptoms are prevalent in SDMs of critically ill patients and are related to role incongruence.

Background The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s (FEV1). Methods From the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1 decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects. Results Fourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, β2-agonists decreased the exercise-induced FEV1 decline by 28 pp., and on the relative scale, they decreased the FEV1 decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28 pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8 pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, β2-agonists reduced exercise-induced FEV1 decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect. Conclusions Compared with the absolute scale, the relative scale captures more effectively the variation in the effects of β2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1 changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.

Objective To determine the safety and efficacy of valve-in-valve transcatheter aortic valve replacement (ViV) versus redo surgical aortic valve replacement (SAVR) for the treatment of previously failed aortic bioprostheses. Background Valve-in-valve has emerged as a treatment option for patients with a failed aortic bioprosthesis. Evidence for safety and efficacy remains limited to small studies. Methods Medline and Embase were searched to 2017 for studies that directly compared ViV to redo SAVR. A random effects meta-analysis was performed. Results Four unadjusted (n = 298) and two propensity-matched (n = 200) observational studies were included. Valve-in-valve patients were 2.85-years older (P = 0.03) and were 23% higher in predicted mortality risk (ratio of means: 1.23, 95% confidence interval (95%CI): 1.02-1.48). There was no difference in peri-operative mortality (4.4% vs. 5.7%, P = 0.83;I2 = 0%) or late mortality, reported at median one year follow-up (incident rate ratio (IRR) 0.93, 95%CI: 0.74-1.16, P = 0.51, I2 = 0%) between ViV and redo SAVR. The incidence of permanent pacemaker implantation (8.3% vs 14.6%; P = 0.05;I2 = 0%) and dialysis (3.2% vs. 10.3%; P = 0.03; I2 = 0%) were lower in ViV. There was a reduction in the incidence of severe patient-prosthesis mismatch (3.3% vs 13.5%; P = 0.03; I2 = 0%) and mild or greater paravalvular leak (5.5% vs 21.1%; P = 0.03; I2 = 37%) in the redo SAVR group compared to ViV. Conclusions Despite higher predicted surgical risk of ViV patients, there was no difference in mortality but less permanent pacemaker implantation and dialysis compared to redo SAVR. Choice of treatment must be individualized for both anatomical and patient risk factors; in high risk patients with favorable previous prosthesis size, valve-in-valve may be preferred.

Background Traditionally, wire cerclage has been used to reapproximate the sternum after sternotomy. Recent evidence suggests that rigid plate fixation for sternal closure may reduce the risk of sternal complications. Methods The Medline and Embase databases were searched from inception to February 2017 for studies that compared rigid plate fixation with wire cerclage for cardiac surgery patients undergoing sternotomy. Random effects meta-analysis compared rates of sternal complications (primary outcome, defined as deep or superficial sternal wound infection, or sternal instability), early mortality, and length of stay (secondary outcomes). Results Three randomized controlled trials (n = 427) and five unadjusted observational studies (n = 1,025) met inclusion criteria. There was no significant difference in sternal complications with rigid plate fixation at a median of 6 months' follow-up (incidence rate ratio 0.51, 95% confidence interval [CI]: 0.20 to 1.29, p = 0.15) overall, but a decrease when including only patients at high risk for sternal complications (incidence rate ratio 0.23, 95% CI: 0.06 to 0.89, p = 0.03; two observational studies). Perioperative mortality was reduced favoring rigid plate fixation (relative risk 0.40, 95% CI: 0.28 to 0.97, p = 0.04; four observational studies and one randomized controlled trial). Length of stay was similar overall (mean difference −0.77 days, 95% CI: −1.65 to +0.12, p = 0.09), but significantly reduced with rigid plate fixation in the observational studies (mean difference −1.34 days, 95% CI: −2.05 to −0.63, p = 0.0002). Conclusions This meta-analysis, driven by the results of unmatched observational studies, suggests that rigid plate fixation may lead to reduced sternal complications in patients at high risk for such events, improved perioperative survival, and decreased hospital length of stay. More randomized controlled trials are required to confirm the potential benefits of rigid plate fixation for primary sternotomy closure.

ObjectiveTo perform a meta-analysis of 4 core CSF biomarkers (β-amyloid [Aβ]42, Aβ40, total tau [t-tau], and phosphorylated tau [p-tau]) to assess which of these are most altered in sporadic cerebral amyloid angiopathy (CAA).MethodsWe systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting amyloid precursor protein metabolism (Aβ42, Aβ40), neurodegeneration (t-tau), and tangle pathology (p-tau) in symptomatic sporadic CAA cohorts vs controls and patients with Alzheimer disease (AD). Biomarker performance was assessed in random-effects meta-analysis based on ratio of mean (RoM) biomarker concentrations: (1) in patients with CAA vs healthy controls and (2) in patients with CAA vs patients with AD. RoM >1 indicates higher biomarker concentration in patients with CAA vs comparison population and RoM ResultsThree studies met inclusion criteria. These comprised 5 CAA patient cohorts (n = 59 patients) vs healthy controls (n = 94 cases) and AD cohorts (n = 158). Three core biomarkers differentiated CAA from controls: CSF Aβ42 (RoM 0.49, 95% confidence interval [CI] 0.38–0.64, p < 0.003), Aβ40 (RoM 0.70, 95% CI 0.63–0.78, p < 0.0001), and t-tau (RoM 1.54, 95% CI 1.15–2.07, p = 0.004); p-tau was marginal (RoM 1.24, 95% CI 0.99–1.54, p = 0.062). Differentiation between CAA and AD was strong for CSF Aβ40 (RoM 0.76, 95% CI 0.69–0.83, p < 0.0001), but not Aβ42 (RoM 1.00; 95% CI 0.81–1.23, p = 0.970). For t-tau and p-tau, average CSF ratios in patients with CAA vs patients with AD were 0.63 (95% CI 0.54–0.74, p < 0.0001) and 0.60 (95% CI 0.50–0.71, p < 0.0001), respectively.ConclusionSpecific CSF patterns of Aβ42, Aβ40, t-tau, and p-tau might serve as molecular biomarkers of CAA, but analyses in larger CAA cohorts are needed.

Background: Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD. Objective: Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF. Methods: Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF concentration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published English articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard errors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) and random effects meta-analysis using Cochrane Collaboration’s Review Manager software. Results: Of the 435 identified publications, after exclusion and removal of duplicates, 35 articles were included comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and metabolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p Conclusion: This study provides proof of concept for the use of meta-analysis validation of AD hypotheses, specifically via robust evidence for the cholinergic hypothesis of AD. Our data disagree with the other synaptic hypotheses of glutamate excitotoxicity and GABAergic resistance to neurodegeneration, given observed unchanged glutamate levels and decreased GABA levels. With regards to metabolic hypotheses, the data supported upregulation of anaerobic glycolysis, pentose phosphate pathway (glutathione), and anaplerosis of the tricarboxylic acid cycle using glutamate. Future applications of meta-analysis indicate the possibility of further in silico evaluation and generation of novel hypotheses in the AD field.

Clinicians' current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described.To describe mechanical ventilation strategies and treatment adjuncts for adults with ARDS, including refractory hypoxemia.This was a prospective cohort study (March 2014-February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring an FiWe enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On Study Day 1, mean Vt was 7.5 (SD = 2.1) ml/kg predicted body weight (n = 625); 80% (n = 501) received Vt greater than 6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cm HPatients with moderate-to-severe ARDS receive treatment adjuncts frequently, especially with refractory hypoxemia. Paradoxically, therapies with less evidence supporting their use (e.g., pulmonary vasodilators) were over-used, whereas those with more evidence (e.g., prone positioning, neuromuscular blockade) were under-used. Patients received higher Vts and lower PEEP than would be suggested by the evidence.

Background Transcatheter aortic valve replacement (TAVR) has emerged as the treatment of choice for patients with severe aortic stenosis at high surgical risk; the role of TAVR compared with surgical aortic valve replacement (SAVR) in the low-intermediate surgical risk population remains uncertain. Our primary objective was to determine differences in 30-day and late mortality in patients treated with TAVR compared with SAVR at low-intermediate risk (Society of Thoracic Surgeons Predicted Risk of Mortality Methods Medline and Embase were searched from 2010 to March 2017 for studies that compared TAVR with SAVR in the low-intermediate surgical risk population, restricted to randomized clinical trials and matched observational studies. Two investigators independently abstracted the data and a random effects meta-analysis was performed. Results Four randomized clinical trials (n = 4042) and 9 propensity score-matched observational studies (n = 4192) were included in the meta-analysis (n = 8234). There was no difference in 30-day mortality between TAVR and SAVR (3.2% vs 3.1%, pooled risk ratio: 1.02; 95% confidence interval, 0.80-1.30; P = 0.89; I 2 = 0%) or mortality at a median of 1.5-year follow-up (incident rate ratio: 1.01; 95% confidence interval, 0.90-1.15; P = 0.83; I 2 = 0%). There was a higher risk of pacemaker implantation and greater than trace aortic insufficiency in the TAVR group whereas the risk of early stroke, atrial fibrillation, acute kidney injury, cardiogenic shock, and major bleeding was higher in the SAVR group. Conclusions Although there was no difference in 30-day and late mortality, the rate of complications differed between TAVR and SAVR in the low-intermediate surgical risk population.

Background Despite their potential interest for clinical management, measurements of respiratory mechanics in patients with acute respiratory distress syndrome (ARDS) are seldom performed in routine practice. We introduced a systematic assessment of respiratory mechanics in our clinical practice. After the first year of clinical use, we retrospectively assessed whether these measurements had any influence on clinical management and physiological parameters associated with clinical outcomes by comparing their value before and after performing the test. Methods The respiratory mechanics assessment constituted a set of bedside measurements to determine passive lung and chest wall mechanics, response to positive end-expiratory pressure, and alveolar derecruitment. It was obtained early after ARDS diagnosis. The results were provided to the clinical team to be used at their own discretion. We compared ventilator settings and physiological variables before and after the test. The physiological endpoints were oxygenation index, dead space, and plateau and driving pressures. Results Sixty-one consecutive patients with ARDS were enrolled. Esophageal pressure was measured in 53 patients (86.9%). In 41 patients (67.2%), ventilator settings were changed after the measurements, often by reducing positive end-expiratory pressure or by switching pressure-targeted mode to volume-targeted mode. Following changes, the oxygenation index, airway plateau, and driving pressures were significantly improved, whereas the dead-space fraction remained unchanged. The oxygenation index continued to improve in the next 48 h. Conclusions Implementing a systematic respiratory mechanics test leads to frequent individual adaptations of ventilator settings and allows improvement in oxygenation indexes and reduction of the risk of overdistention at the same time. Trial registration The present study involves data from our ongoing registry for respiratory mechanics (ClinicalTrials.gov identifier: NCT02623192. Registered 30 July 2015). Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1671-8) contains supplementary material, which is available to authorized users.

Objectives This meta-analysis compares total arterial revascularization (TAR) versus conventional coronary artery bypass and additionally to two arterial grafts. Methods We searched MEDLINE and EMBASE Databases from 1996-to-2016 for studies comparing TAR versus non-TAR for multi-vessel surgical revascularization. Data were extracted by 2 independent investigators. Meta-analysis used random effects, which incorporates heterogeneity. Results There were 4 smaller shorter follow-up randomized controlled trials (RCTs), plus 15 matched/adjusted and 6 unmatched/unadjusted larger longer follow-up observational studies that met inclusion criteria ( N =130.305 patients; mean follow-up range: 1–15years). There were no differences in perioperative stroke, myocardial infarction or mortality. However, TAR was associated with lower long term all-cause mortality in observational studies matched/adjusted for confounders (incident rate ratio 0.85, 95% CI: 0.81–0.89, p I 2 =0%) and unmatched/unadjusted (incident rate ratio 0.67, 95% CI: 0.59–0.76, p I 2 =67%) for TAR. Decreases in major cardiovascular outcomes and revascularization did not achieve statistical significance. There were greater sternal complications with TAR in the matched/adjusted studies (pooled risk ratio 1.21, 95% CI: 1.03–1.42, p =0.02; I 2 =0%). When compared to patients with two arterial grafts, TAR was still associated with reduced long-term all-cause mortality (incident rate ratio 0.85, 95% CI: 0.73–0.99, p =0.04) with minimal heterogeneity ( I 2 =5%). Conclusions Data from primarily observational studies suggest that TAR may improve long-term survival compared with conventional coronary bypass by 15–20% even when compared with two arterial grafts. Prospective randomized trials of TAR with long term follow-up are needed.

Background Given recent discrepant results from randomized controlled trials (RCTs), we examined the totality of RCT evidence assessing the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and heart failure. Methods MEDLINE, Embase and ClinicalTrials.gov were searched without language restrictions to August 2016 for RCTs comparing DPP-4 inhibitors to placebo or no therapy for a period of 24 weeks or more. We included all heart failure outcomes when listed either as a serious adverse event or adverse event. Pooled analyses used random-effects. Results We identified 100 RCTs (n = 79 867) - 3 large cardiovascular-safety RCTs (SAVOR-TIMI 53[saxagliptin]/n = 16 492, EXAMINE[alogliptin]/n = 5380, and TECOS[sitagliptin]/n = 14 735), and 97 smaller RCTs with a primary outcome that was usually change in glycated hemoglobin. Virtually all RCTs were high-quality, multicentre, placebo-controlled trials. A total of 96% (1192/1244) of heart failure events were prespecified, blindly adjudicated and required hospital admission. Pooled results suggested a 13% increase in heart failure (relative risk [RR] 1.13, 95% confidence interval [CI] 1.01-1.26, I2 = 0%; 32 RCTs, n = 54 640, 1244 events). When including only the 3 large RCTs, the increase was similar, but not significant (RR 1.14, 95% CI 0.97-1.32; 3 RCTs, n = 36 543, 1169 adjudicated events; number needed to harm 246) owing to heterogeneity (I2 = 42%), which lead to wider CIs, because SAVOR-TIMI 53 showed increased heart failure (RR 1.26, 95% CI 1.06-1.49) and TECOS showed no effect (RR 1.00, 95% CI 0.83-1.19). Interpretation Despite pooled data from 79 867 patients, whether DPP-4 inhibitors increase heart failure overall or exhibit within-class differences remains unresolved. Our results highlight the importance of ongoing trials that are comparing DPP-4 inhibitors to placebo, although no large cardiovascular-safety RCTs are comparing different DPP-4 inhibitors to each other; consequently, these will address the overall but not class-difference question.

Background Blood transfusion is a well-established independent risk factor for mortality in patients undergoing cardiac surgery but the impact of platelet transfusion is less clear. We performed a systematic review and meta-analysis of observational studies comparing outcomes of patients who received platelet transfusion after cardiac surgery. Methods We searched MEDLINE and EMBASE databases to January 2019 for studies comparing perioperative outcomes in patients undergoing cardiac surgery with and without platelet transfusion. Results There were nine observational studies reporting 101,511 patients: 12% with and 88% without platelet transfusion. In unmatched/unadjusted studies, patients who received platelet transfusion were older, with greater incidence of renal, peripheral, and cerebrovascular disease, myocardial infarction, left ventricular dysfunction, and anemia. They were more likely to have nonelective, combined surgery; preoperative hemodynamic instability and endocarditis; and more likely to be receiving clopidogrel preoperatively. Perioperative complications were significantly increased without adjusting for these baseline differences. After pooling only matched/adjusted data, differences were not found between patients who did receive platelets and patients who did not in operative mortality (risk ratio [RR] 1.26; 95% confidence interval [CI], 0.69 to 2.32, P = .46, five studies), stroke (RR 0.94; 95% CI, 0.62 to 1.45; P = .79; five studies), myocardial infarction (RR 1.29; 95% CI, 0.95 to 1.77; P = .11; three studies), reoperation for bleeding (RR 1.20; 95% CI, 0.46 to 3.18; P = .71; three studies), infection (RR 1.02; 95% CI, 0.86 to 1.20; P = .85; six studies); and perioperative dialysis (RR 0.91; 95% CI, 0.63 to 1.32; P = .62; three studies). Conclusions After accounting for baseline differences, platelet transfusion was not linked with perioperative complications in cardiac surgery patients. Given the small number of observational studies, these findings should be considered hypothesis generating.

Background ICU survivors can experience both cognitive dysfunction and persistent sleep disturbances after hospitalization. Sleep disturbances have been linked with cognitive impairment in various patient populations, and the apolipoprotein E (APOE) genotype has been linked to sleep-related impairments in cognition. Research Question Is there an association between sleep, long-term cognition, and APOE status in ICU survivors? Study Design and Methods We enrolled 150 patients from five centers who had been mechanically ventilated for at least 3 days; 102 patients survived to ICU discharge. Actigraphy and cognitive testing were undertaken at 7 days, 6 months, and 12 months after ICU discharge, and sleep duration, quality, and timing were estimated by actigraphy. APOE single nucleotide polymorphisms were assessed for each patient. Results Actigraphy-estimated sleep fragmentation, but not total sleep time or interdaily stability (estimate of circadian rhythmicity), was associated with worse cognitive impairment at 7 days of ICU discharge. No actigraphy-estimated variable of sleep estimation at 7 days post-ICU discharge predicted cognitive impairment or persistent sleep abnormalities at 6 and 12 months of follow-up in subsequently assessed survivors. Possessing the APOE e4 allele was not significantly associated with sleep disturbances and its presence did not modify the risk of sleep-related cognitive impairment at follow-up. Interpretation Sleep fragmentation estimated by actigraphy was associated with worse cognitive performance in hospital, but not at later time intervals. Further research is needed to better delineate the relationship between persistent sleep disturbances and cognition in larger numbers of ICU survivors. Trial Registry ClinicalTrials.gov ; No.: NCT02086877; URL: www.clinicaltrials.gov

The purpose of the study was to provide a systematic review of the literature reporting the contemporary early outcomes after endovascular and open repair of thoracoabdominal aortic aneurysms (TAAAs).MEDLINE and Embase were searched for studies from January 2006 to March 2018 that reported either endovascular (using branched or fenestrated endografts) or open repair of TAAA in at least 10 patients. Outcomes of interest included perioperative mortality, spinal cord injury (SCI), renal failure requiring dialysis, and stroke. Pooled proportions were determined using a random-effects model.The analysis included 71 studies, of which 24 and 47 reported outcomes after endovascular and open TAAA repair, respectively. Endovascular cohort patients were older and had higher rates of coronary artery disease, chronic obstructive pulmonary disease, and diabetes. Endovascular repair was associated with higher rates of SCI (13.5%; 95% confidence interval [CI], 10.5%-16.7%) compared with open repair (7.4%; 95% CI, 6.2%-8.7%; P .01) but similar rates of permanent paralysis (5.2% [95% CI, 3.8%-6.7%] vs 4.4% [95% CI, 3.3%-5.6%]; P = .39), lower rates of postoperative dialysis (6.4% [95% CI, 3.2%-9.5%] vs 12.0% [95% CI, 8.2%-16.3%]; P = .03) but similar rates of being discharged on permanent dialysis (3.7% [95% CI, 2.0%-5.9%] vs 3.8% [95% CI, 2.9%-5.3%]; P = .93), a trend to lower stroke (2.7% [95% CI, 1.9%-3.6%] vs 3.9% [95% CI, 3.0%-4.9%]; P = .06), and similar perioperative mortality (7.4% [95% CI, 5.9%-9.1%] vs 8.9% [95% CI, 7.2%-10.9%]; P = .21).This systematic review summarizes the contemporary literature results of endovascular and open TAAA repair. Endovascular repair studies included patients with more comorbidities and were associated with higher rates of SCI but similar rates of permanent paraplegia, whereas open repair studies had higher rates of postoperative dialysis but similar rates of being discharged on permanent dialysis. Perioperative mortality rates were similar. Universally adopted reporting standards for patient characteristics, outcomes, and the conduct of contemporary comparative studies will allow better assessment and comparisons of the risks associated with the two surgical treatment options for TAAA.

Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design.To stratify patients for post-ICU disability and recovery to 1 year after critical illness.We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling.The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year.ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00896220).

There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality. Despite the availability of clinical practice guidelines for the management of acute pancreatitis, recent studies auditing the clinical management of the condition have shown important areas of noncompliance with evidence-based recommendations. This underscores the importance of creating understandable and implementable recommendations for the diagnosis and management of acute pancreatitis. The purpose of the present guideline is to provide evidence-based recommendations for the management of both mild and severe acute pancreatitis as well as the management of complications of acute pancreatitis and of gall stone-induced pancreatitis.Une hausse de l’incidence de pancréatite aiguë a été constatée à l’échelle mondiale. Malgré l’amélioration de l’accès aux soins et aux techniques d’imagerie et d’intervention, la pancréatite aiguë est toujours associée à une morbidité et une mortalité importantes. Bien qu’il existe des guides de pratique clinique pour la prise en charge de la pancréatite aiguë, des études récentes sur la vérification de la prise en charge clinique de cette affection révèlent des lacunes importantes dans la conformité aux recommandations fondées sur des données probantes. Ces résultats mettent en relief l’importance de formuler des recommandations compréhensibles et applicables pour le diagnostic et la prise en charge de la pancréatite aiguë. La présente ligne directrice vise à fournir des recommandations fondées sur des données probantes pour la prise en charge de la pancréatite aiguë, qu’elle soit bénigne ou grave, ainsi que de ses complications et de celles de la pancréatite causée par un calcul biliaire.

Background: While proportional assist ventilation (PAV), generates pressure in proportion to effort without a preselected target, proportional assist ventilation plus (PAV+) measures compliance and resistance, calculates work of breathing, and adjusts support to a preset assistance level. Objective: To summarize randomized controlled trials (RCTs) comparing invasive or noninvasive PAV or PAV+ in critically ill patients. Data Sources: We searched multiple databases to April 2017 without language restrictions and conference proceedings from 5 meetings to identify randomized parallel-group and crossover RCTs that compared invasive or noninvasive PAV or PAV+ to another mode in critically ill adults or children and reported at least 1 clinically important outcome. Results: We identified 14 RCTs (11 parallel group and 3 crossover) assessing PAV (n = 7) and PAV+ (n = 7) involving 931 adult patients. We found no effect of noninvasive PAV (vs noninvasive pressure support [PS]) on intubation (risk ratio 0.92 [0.59 to 1.43], I2 = 0%) or invasive PAV (vs invasive PS) on percentage rapid eye movement sleep (mean difference [MD] −2.93% [−14.20 to ±8.34], I2 = 43%). Compared to invasive PS, invasive PAV+ showed a nonsignificant increase in weaning time (MD +0.54 [−0.67 to +1.75] hours, I2 = 0%), but no effect on hospital mortality, reintubation, or tracheostomy. Conclusions: Current evidence does not support the use of invasive or noninvasive PAV or invasive PAV+ in critically ill adults. Amid low to moderate heterogeneity, we identified 3 promising areas for future research including assessing the role of noninvasive PAV as an initial support strategy in patients with acute respiratory failure, invasive PAV on sleep quality during invasive ventilation, and possibly invasive PAV+ for weaning.

Objective The objective of this study was to compare the early results of endovascular vs open thoracoabdominal aortic aneurysm (TAAA) repair. Methods MEDLINE and Embase were searched for studies from January 2006 to March 2018 that compared endovascular vs open repair of TAAA using branched or fenestrated endografts. Data were subjected to a meta-analysis using a random-effects model. The outcomes of interest included early mortality, spinal cord injury, renal failure requiring dialysis, stroke, and hospital length of stay. Results Eight comparative studies met inclusion criteria. There were two retrospective propensity-matched studies, two unadjusted single-center retrospective studies, and four unadjusted national population-based studies. Mortality in the matched studies was equivalent in both groups. Pooled analysis of all unmatched observational studies revealed a survival benefit for endovascular over open repair (relative risk [RR], 0.63; 95% confidence interval [CI],0.45-0.87); P Conclusions There are few reports comparing endovascular vs open repair of TAAAs. Short-term outcomes may be improved in patients undergoing endovascular treatment of TAAA on the basis of a limited number of studies with high risk of bias. These findings highlight the need for larger comparative studies with standardization of reporting.

Background Surgical timing in infective endocarditis (IE) with preoperative neurological events remains controversial. The relevant society guidelines are each on the basis of a small number of observational studies. This meta-analysis was designed to search the available literature broadly and assess the weight of available evidence as comprehensively as possible. Methods We searched MEDLINE and EMBASE to April 2018 for studies that compared mortality or neurological exacerbation in early vs late surgery for IE complicated by neurological events. Random effects meta-analysis was performed. Results Twenty-seven observational studies (25 unadjusted, n = 879; 2 adjusted, n = 451) met inclusion criteria. Using early and late thresholds defined in each study (7 or 14 days), early surgery in ischemic or hemorrhagic stroke was associated with elevated perioperative mortality vs late surgery (pooled relative risk [RR], 1.74; 95% confidence interval, 1.34-2.25; P Conclusions Available observational data support delaying surgery by 7-14 days if possible in IE complicated by ischemic stroke and > 21 days in hemorrhagic stroke to decrease perioperative mortality and neurological exacerbation rates. Randomized trials are needed for definitive guidance.

Introduction There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. Methods We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl]

Background: Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions. The interpretation of the magnitude of these differences — from trivial to large — can, however, be challenging. We investigated clinicians’ understanding and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses (standardized mean difference, minimal important difference units, mean difference in natural units, ratio of means, relative risk and risk difference). Methods: We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate. Paper-based, self-administered questionnaires presented summary estimates of hypothetical interventions versus placebo for chronic pain. The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes. Questions addressed participants’ understanding of the magnitude of treatment effects and their perception of the usefulness of the presentation format. We randomly assigned participants 1 of 4 versions of the questionnaire, each with a different effect size (large or small) and presentation order for the 6 formats (1 to 6, or 6 to 1). Results: Overall, 531 (87.0%) of the clinicians responded. Respondents best understood risk difference, followed by relative risk and ratio of means. Similarly, they perceived the dichotomous presentation of continuous outcomes (relative risk and risk difference) to be most useful. Presenting results as a standardized mean difference, the longest standing and most widely used approach, was poorly understood and perceived as least useful. Interpretation: None of the presentation formats were well understood or perceived as extremely useful. Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful. Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed.

Post-operative atrial fibrillation (POAF) still occurs commonly after cardiac surgery and is associated with stroke, congestive heart failure, acute kidney injury, and death [(1)][1]. A comprehensive framework for management of POAF should include: 1) modification of potential triggers and

Background The effect of alternative spontaneous breathing trial (SBT) techniques on extubation success and other clinically important outcomes is uncertain. Methods We searched MEDLINE, EMBASE, CENTRAL, CINAHL, Evidence-Based Medicine Reviews, Ovid Health Star, proceedings of five conferences (1990–2016), and reference lists for randomized trials comparing SBT techniques in intubated adults or children. Primary outcomes were initial SBT success, extubation success, or reintubation. Two reviewers independently screened citations, assessed trial quality, and abstracted data. Results We identified 31 trials (n = 3541 patients). Moderate-quality evidence showed that patients undergoing pressure support (PS) compared with T-piece SBTs (nine trials, n = 1901) were as likely to pass an initial SBT (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.89–1.11; I 2 = 77%) but more likely to be ultimately extubated successfully (RR 1.06, 95% CI 1.02–1.10; 11 trials, n = 1904; I 2 = 0%). Exclusion of one trial with inconsistent results for SBT and extubation outcomes suggested that PS (vs T-piece) SBTs also improved initial SBT success (RR 1.06, 95% CI 1.01–1.12; I 2 = 0%). Limited data suggest that automatic tube compensation plus continuous positive airway pressure (CPAP) vs CPAP alone or PS increase SBT but not extubation success. Conclusions Patients undergoing PS (vs T-piece) SBTs appear to be 6% (95% CI 2–10%) more likely to be extubated successfully and, if the results of an outlier trial are excluded, 6% (95% CI 1–12%) more likely to pass an SBT. Future trials should investigate patients for whom SBT and extubation outcomes are uncertain and compare techniques that maximize differences in support. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1698-x) contains supplementary material, which is available to authorized users.

Background Little is known about homeless patients in intensive care units (ICUs). Objectives To compare clinical characteristics, treatments, and outcomes of homeless to non-homeless patients admitted to four ICUs in a large inner-city academic hospital. Methods 63 randomly-selected homeless compared to 63 age-, sex-, and admitting-ICU-matched non-homeless patients. Results Compared to matched non-homeless, homeless patients (average age 48±12 years, 90% male, 87% admitted by ambulance, 56% mechanically ventilated, average APACHE II 17) had similar comorbidities and illness severity except for increased alcohol (70% vs 17%,p

Purpose:We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of high-flow nasal cannula (HFNC) on reintubation in adult patients.Procedures:Ovid Medline, Embase, and Cochrane Database of Systematic Reviews were searched up to November 1, 2016, for RCTs comparing HFNC versus conventional oxygen therapy (COT) or noninvasive ventilation (NIV) in adult patients after extubation. The primary outcome was reintubation rate, and the secondary outcomes included complications, tolerance and comfort, time to reintubation, length of stay, and mortality. Dichotomous outcomes were presented as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as weighted mean difference and 95% CIs. The random effects model was used for data pooling.Findings:Seven RCTs involving 2781 patients were included in the analysis. The HFNC had a similar reintubation rate compared to either COT (RR, 0.58; 95% CI, 0.21-1.60; P = .29; 5 RCTs, n = 1347) or NIV (RR, 1.11; 95% CI, 0.88-1.40; P = .37; 2 RCTs, n = 1434). In subgroup of critically ill patients, the HFNC group had a significantly lower reintubation rate compared to the COT group (RR, 0.35; 95% CI, 0.19-0.64; P = .0007; 2 RCTs, n = 632; interaction P = .07 compared to postoperative subgroup). Qualitative analysis suggested that HFNC might be associated with less complications and improved patient’s tolerance and comfort. The HFNC might not delay reintubation. Trial sequential analysis on the primary outcome showed that required information size was not reached.Conclusion:The evidence suggests that COT may still be the first-line therapy in postoperative patients without acute respiratory failure. However, in critically ill patients, HFNC may be a potential alternative respiratory support to COT and NIV, with the latter often associating with patient intolerance and requiring a monitored setting. Because required information size was not reached, further high-quality studies are required to confirm these results.

Recognizing patients in whom endotracheal intubation is likely to be difficult can help alert physicians to the need for assistance from a clinician with airway training and having advanced airway management equipment available.To identify risk factors and physical findings that predict difficult intubation.The databases of MEDLINE and EMBASE were searched from 1946 to June 2018 and from 1947 to June 2018, respectively, and the reference lists from the retrieved articles and previous reviews were searched for additional studies.Sixty-two studies with high (level 1-3) methodological quality that evaluated the accuracy of clinical findings for identifying difficult intubation were reviewed.Two authors independently abstracted data. Bivariate random-effects meta-analyses were used to calculate summary positive likelihood ratios across studies or univariate random-effects models when bivariate models failed to converge.Among the 62 high-quality studies involving 33 559 patients, 10% (95% CI, 8.2%-12%) of patients were difficult to intubate. The physical examination findings that best predicted a difficult intubation included a grade of class 3 on the upper lip bite test (lower incisors cannot extend to reach the upper lip; positive likelihood ratio, 14 [95% CI, 8.9-22]; specificity, 0.96 [95% CI, 0.93-0.97]), shorter hyomental distance (range of3-5.5 cm; positive likelihood ratio, 6.4 [95% CI, 4.1-10]; specificity, 0.97 [95% CI, 0.94-0.98]), retrognathia (mandible measuring9 cm from the angle of the jaw to the tip of the chin or subjectively short; positive likelihood ratio, 6.0 [95% CI, 3.1-11]; specificity, 0.98 [95% CI, 0.90-1.0]), and a combination of physical findings based on the Wilson score (positive likelihood ratio, 9.1 [95% CI, 5.1-16]; specificity, 0.95 [95% CI, 0.90-0.98]). The widely used modified Mallampati score (≥3) had a positive likelihood ratio of 4.1 (95% CI, 3.0-5.6; specificity, 0.87 [95% CI, 0.81-0.91]).Although several simple clinical findings are useful for predicting a higher likelihood of difficult endotracheal intubation, no clinical finding reliably excludes a difficult intubation. An abnormal upper lip bite test, which is easily assessed by clinicians, raises the probability of difficult intubation from 10% to greater than 60% for the average-risk patient.

Spontaneous breathing trials (SBTs) are designed to simulate conditions after extubation, and it is essential to understand the physiologic impact of different methods.We conducted a systematic review and pooled measures reflecting patient respiratory effort among studies comparing SBT methods in a meta-analysis.We searched Medline, Excerpta Medica Database, and Web of Science from inception to January 2016 to identify randomized and nonrandomized clinical trials reporting physiologic measurements of respiratory effort (pressure-time product) or work of breathing during at least two SBT techniques. Secondary outcomes included the rapid shallow breathing index (RSBI), and effort measured before and after extubation. The quality of physiologic measurement and research design was appraised for each study. Outcomes were analyzed using ratio of means.Among 4,138 citations, 16 studies (n = 239) were included. Compared with T-piece, pressure support ventilation significantly reduced work by 30% (ratio of means [RoM], 0.70; 95% confidence interval [CI], 0.57-0.86), effort by 30% (RoM, 0.70; 95% CI, 0.60-0.82), and RSBI by 20% (RoM, 0.80; 95% CI, 0.75-0.86). Continuous positive airway pressure had significantly lower pressure-time product by 18% (RoM, 0.82; 95% CI, 0.68-0.999) compared with T-piece, and reduced RSBI by 16% (RoM, 0.84; 95% CI, 0.74-0.95). Studies comparing SBTs with the postextubation period demonstrated that pressure support induced significantly lower effort and RSBI; T-piece reduced effort, but not the work, compared with postextubation. Work, effort, and RSBI measured while intubated on the ventilator with continuous positive airway pressure of 0 cm HPressure support reduces respiratory effort compared with T-piece. Continuous positive airway pressure of 0 cm H

To evaluate whether a Post-Arrest Consult Team improved care and outcomes for patients with out-of-hospital cardiac arrest.Prospective cohort study of Post-Arrest Consult Team implementation at two hospitals, with concurrent controls from 27 others.Twenty-nine hospitals within the Strategies for Post-Arrest Care Network of Southern Ontario, Canada.We included comatose adult nontraumatic out-of-hospital cardiac arrest patients surviving more than or equal to 6 hours after emergency department arrival who had no contraindications to targeted temperature management.The Post-Arrest Consult Team was an advisory consult service to improve 1) targeted temperature management, 2) assessment for percutaneous coronary intervention, 3) electrophysiology assessment, and 4) appropriately delayed neuroprognostication.We used generalized linear mixed models to explore the association between Post-Arrest Consult Team implementation and performance of targeted processes. We included 1,006 patients. The Post-Arrest Consult Team was associated with a significant reduction over time in rates of withdrawal of life-sustaining therapy within 72 hours of emergency department arrival on the basis of predictions of poor neurologic prognosis (ratio of odds ratios, 0.13; 95% CI, 0.02-0.98). Post-Arrest Consult Team was not associated with improved successful targeted temperature management (ratio of odds ratios, 0.91; 95% CI, 0.31-2.65), undergoing angiography (ratio of odds ratios, 1.91; 95% CI, 0.17-21.04), receiving electrophysiology consultation (ratio of odds ratios, 0.93; 95% CI, 0.11-8.16), or functional survival (ratio of odds ratios, 0.75; 95% CI, 0.19-2.94).Implementation of a Post-Arrest Consult Team reduced premature withdrawal of life-sustaining therapy but did not improve rates of successful targeted temperature management, coronary angiography, formal electrophysiology assessments, or functional survival for comatose patients after out-of-hospital cardiac arrest.

Background Despite the high mortality in patients with pneumonia admitted to an ICU, data on risk factors for death remain limited. Methods In this secondary analysis of PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial), we focused on the patients admitted to ICU with a primary diagnosis of pneumonia. The primary outcome for this study was 90-day hospital mortality and the secondary outcome was 90-day ICU mortality. Cox regression model was conducted to examine the relationship between baseline and time-dependent variables and hospital and ICU mortality. Results Six hundred sixty seven patients admitted with pneumonia (43.8 % females) were included in our analysis, with a mean age of 60.7 years and mean APACHE II score of 21.3. During follow-up, 111 patients (16.6 %) died in ICU and in total, 149 (22.3 %) died in hospital. Multivariable analysis demonstrated significant independent risk factors for hospital mortality including male sex (hazard ratio (HR) = 1.5, 95 % confidence interval (CI): 1.1 - 2.2, p-value = 0.021), higher APACHE II score (HR = 1.2, 95 % CI: 1.1 - 1.4, p-value