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BACKGROUND Clinicians use several measures to ascertain whether individual patients will tolerate liberation from mechanical ventilation, including the rapid shallow breathing index (RSBI). RESEARCH QUESTION Given varied use of different thresholds, patient populations, and measurement characteristics, how well does RSBI predict successful extubation? STUDY DESIGN AND METHODS We searched six databases from inception through September 2019 and selected studies reporting the accuracy of RSBI in the prediction of successful extubation. We extracted study data and assessed quality independently and in duplicate. RESULTS We included 48 studies involving RSBI measurements of 10,946 patients. Pooled sensitivity for RSBI of < 105 in predicting extubation success was moderate (0.83 [95% CI, 0.78-0.87], moderate certainty), whereas specificity was poor (0.58 [95% CI, 0.49-0.66], moderate certainty) with diagnostic ORs (DORs) of 5.91 (95% CI, 4.09-8.52). RSBI thresholds of < 80 or 80 to 105 yielded similar sensitivity, specificity, and DOR. These findings were consistent across multiple subgroup analyses reflecting different patient characteristics and operational differences in RSBI measurement. INTERPRETATION As a stand-alone test, the RSBI has moderate sensitivity and poor specificity for predicting extubation success. Future research should evaluate its role as a permissive criterion to undergo a spontaneous breathing trial (SBT) for patients who are at intermediate pretest probability of passing an SBT. TRIAL REGISTRY PROSPERO; No.: CRD42020149196.

We evaluated characteristics associated with neuromuscular blockade (NMB) use, center-level variation, and whether NMB mediated excess mortality among patients assigned to high-frequency oscillatory ventilation (HFOV) in the OSCILLATE trial.NMB exposure was defined as receipt after randomization; the primary outcome was hospital mortality. Descriptive analyses compared NMB-exposed vs unexposed patients. Multivariable analyses included patients not on baseline NMB. Cox regression evaluated associations of patient- and center-level variables with NMB use. A log-normal frailty model evaluated center effects. Mediation analysis examined the effect of NMB in HFOV-assigned patients.376/548 patients (39 centers) received post-randomization NMB, of whom 165 received baseline NMB. Patients receiving post-randomization NMB (vs. not) had worse lung mechanics and gas exchange, received more sedation and vasopressors (p 0.05), and had higher hospital mortality (44% vs. 34%, p = 0.03). Mean airway pressure ≥ 24 cmHIn OSCILLATE, receipt of post-randomization NMB was associated with worse outcomes, but NMB use did not mediate HFOV-associated higher mortality.

Rationale: Choosing the best ventilation strategy for acute respiratory distress syndrome (ARDS) is complex, yet it is highly relevant to clinicians during a respiratory pandemic. Objectives: To co...

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.

BackgroundCritically ill patients receive frequent routine and recurring blood tests, some of which are unnecessary.AimTo reduce unnecessary routine phlebotomy in a 30-bed tertiary medical-surgical intensive care unit (ICU) in Toronto, Ontario.MethodsThis prospective quality improvement study included a 7-month preintervention baseline, 5-month intervention and 11-month postintervention period. Change strategies included education, ICU rounds checklists, electronic order set modifications, an electronic test add-on tool and audit and feedback. The primary outcome was mean volume of blood collected per patient-day. Secondary outcomes included the number blood tubes used and red cell transfusions. Balancing measures included the timing and types of blood tests, ICU length of stay and mortality. Outcomes were evaluated using process control charts and segmented regression.ResultsPatient demographics did not differ between time periods; total number of patients: 2096, median age: 61 years, 60% male. Mean phlebotomy volume±SD decreased from 41.1±4.0 to 34.1±4.7 mL/patient-day. Special cause variation was met at 13 weeks. Segmental regression demonstrated an immediate postintervention decrease of 6.6 mL/patient-day (95% CI 1.8 to 11.4 p=0.009), which was sustained. Blood tube consumption decreased by 1.4 tubes/patient-day (95% CI 0.4 to 2.4, p=0.005) amounting to 13 276 tubes (95% CI 4602 to 22 127 tubes) saved over 11 months. Red blood cell transfusions decreased from 10.5±5.2 to 8.3±4.4 transfusions/100 patient-days (incident rate ratio 0.56, 95% CI 0.35 to 0.88, p=0.01). There was no impact on length of stay (2 days, IQR 1–5) and mortality (18.1%±2.0%).ConclusionIterative improvement interventions targeting clinician test ordering behaviour can reduce ICU phlebotomy and may impact red cell transfusions. Frequent stakeholder consultation, incorporating stewardship into daily workflow, and audit and feedback are effective strategies.

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

Key Points Question Do clinical practice guidelines (CPGs) that report on pharmacologic treatments of hospitalized patients with COVID-19 meet the National Academy of Medicine standards for trustworthiness? Findings In this systematic review of 32 CPGs of predominantly low quality, few reported funding sources or conflicts of interest, included a methodologist, described a search strategy or study selection process, or synthesized evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated the confidence in the quality of the evidence (6 [18.8%]), described potential benefits and harms (6 [18.8%]), or graded the strength of recommendations (5 [15.6%]). Meaning The findings of this study suggest that few COVID-19 CPGs meet National Academy of Medicine standards for trustworthy guidelines., This systematic review evaluates the quality and trustworthiness of clinical practice guidelines for pharmacologic treatment of hospitalized patients with COVID-19 using the National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards instrument., Importance The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission. Objective To appraise the quality of clinical practice guidelines (CPGs) using the National Academy of Medicine (NAM) criteria. Evidence Review A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument. Findings Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 [18.8%]), described potential benefits and harms (6 of 32 [18.8%]), or graded the strength of the recommendations (5 of 32 [15.6%]). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions. Conclusions and Relevance In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges. Trial Registration PROSPERO Identifier: CRD42021245239

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.

IMPORTANCE: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. OBJECTIVE: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). INTERVENTIONS: Enteral L rhamnosus GG (1 × 10(10) colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. MAIN OUTCOMES AND MEASURES: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. RESULTS: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, –2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P

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.

BackgroundExtubation to non-invasive ventilation (NIV) has been investigated as a strategy to wean critically ill adults from invasive ventilation and reduce ventilator-related complications.MethodsWe searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, proceedings of four conferences and bibliographies (to June 2020) for randomised and quasi-randomised trials that compared extubation with immediate application of NIV to continued invasive weaning in intubated adults and reported mortality (primary outcome) or other outcomes. Two reviewers independently screened citations, assessed trial quality and abstracted data.ResultsWe identified 28 trials, of moderate-to-good quality, involving 2066 patients, 44.6% with chronic obstructive pulmonary disease (COPD). Non-invasive weaning significantly reduced mortality (risk ratio (RR) 0.57, 95% CI 0.44 to 0.74; high quality), weaning failures (RR 0.59, 95% CI 0.43 to 0.81; high quality), pneumonia (RR 0.30, 95% CI 0.22 to 0.41; high quality), intensive care unit (ICU) (mean difference (MD) −4.62 days, 95% CI −5.91 to −3.34) and hospital stay (MD −6.29 days, 95% CI −8.90 to −3.68). Non-invasive weaning also significantly reduced the total duration of ventilation, duration of invasive ventilation and duration of ventilation related to weaning (MD −0.57, 95% CI −1.08 to −0.07) and tracheostomy rate. Mortality, pneumonia, reintubation and ICU stay were significantly lower in trials enrolling COPD (vs mixed) populations.ConclusionNon-invasive weaning significantly reduced mortality, pneumonia and the duration of ventilation related to weaning, particularly in patients with COPD. Beneficial effects are less clear (or more careful patient selection is required) in non-COPD patients.PROSPERO registration numberCRD42020201402.

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.).

Left ventricular assist device (LVAD) implantation via lateral thoracotomy can offer similar effectiveness to conventional approaches with less perioperative adverse events. We performed a systematic review and meta-analysis to determine the potential benefits of lateral thoracotomy (LT) for LVAD implantation compared to median sternotomy.We searched MEDLINE and Embase databases for studies comparing continuous-flow LVAD implantation using LT with conventional sternotomy. Main outcomes were perioperative mortality and complications.Twenty-five observational studies enrolling 3072 patients were included with a median follow-up of 10 months. Perioperative mortality (30 day or in-hospital) was 7% (LT) and 14% (sternotomy); however, mortality differences were no longer statistically significant in matched/adjusted studies (RR:0.86; 95%CI:0.52-1.44; p = 0.58). LT was associated with decreased need for blood product transfusions (mean difference[MD]: -4.7; 95%CI: -7.2 to -2.3 units; p0.001), reoperation for bleeding (RR:0.34; 95%CI:0.22-0.54; p0.001), postoperative RVAD implantation (RR:0.53; 95%CI:0.36-0.77; p0.001), days requiring inotropes (MD: -1.1; 95%CI: -2.1 to -0.03 inotrope days; p = 0.04), ICU (MD: -3.3; 95%CI: -6.0 to -0.7 ICU days; p = 0.01), and hospital length of stay (MD: -5.1; 95%CI: -10.1 to -0.1 hospital days; p = 0.04) in matched/adjusted studies. Overall mortality during follow-up was significantly lower for LT in unmatched/unadjusted studies but not statistically significantly lower in matched/adjusted studies (Hazard Ratio:0.82; 95%CI:0.59-1.14; p = 0.24).LVAD implantation via LT was associated with significantly decreased need for blood products, reoperation for bleeding, and postoperative RVAD implantation. Furthermore, days on inotropic support were also lower, likely contributing to the shorter length of stay. These findings support greater use of a LT approach for carefully selected patients.

Background Prolonged need for mechanical ventilation greatly impacts life expectancy of patients after spinal cord injury (SCI). Weaning outcomes have never been systematically assessed. In this systematic review and meta-analysis, we aimed to investigate the probability of weaning success, duration of mechanical ventilation, mortality, and their predictors in mechanically ventilated patients with SCI. Methods We searched six databases from inception until August 2021 for randomized-controlled trials and observational studies enrolling adult patients (≥ 16 years) with SCI from any cause requiring mechanical ventilation. Titles and abstracts were screened independently by two reviewers. Full texts of the identified articles were then assessed for eligibility. Data were extracted independently and in duplicate by pairs of authors, using a standardized data collection form. Synthetic results are reported as meta-analytic means and proportions, based on random effects models. Results Thirty-nine studies (14,637 patients, mean age 43) were selected. Cervical lesions were predominant (12,717 patients had cervical lesions only, 1843 in association with other levels’ lesions). Twenty-five studies were conducted in intensive care units (ICUs), 14 in rehabilitative settings. In ICU, the mean time from injury to hospitalization was 8 h [95% CI 7–9], mean duration of mechanical ventilation 27 days [20–34], probability of weaning success 63% [45–78] and mortality 8% [5–11]. Patients hospitalized in rehabilitation centres had a greater number of high-level lesions (C3 or above), were at 40 days [29–51] from injury and were ventilated for a mean of 97 days [65–128]; 82% [70–90] of them were successfully weaned, while mortality was 1% [0–19]. Conclusions Although our study highlights the lack of uniform definition of weaning success, of clear factors associated with weaning outcomes, and of high-level evidence to guide optimal weaning in patients with SCI, it shows that around two-thirds of mechanically ventilated patients can be weaned in ICU after SCI. A substantial gain in weaning success can be obtained during rehabilitation, with additional duration of stay but minimal increase in mortality. The study is registered with PROSPERO (CRD42020156788).

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.

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.RéSUMé: Ce compte rendu narratif évalue de façon critique les données probantes concernant le risque de l’anémie et de la transfusion d’érythrocytes. Pour ce faire, nous avons évalué des études randomisées contrôlées (ERC) prospectives de grande envergure réalisées auprès de populations de patients médicaux, chirurgicaux et de soins intensifs dans lesquelles l’impact de seuils spécifiques de transfusion d’hémoglobine est comparé. Dans ces études, les risques de l’anémie sont comparés aux risques de la transfusion d’érythrocytes. Les résultats des comptes rendus systématiques et méta-analyses publiés sont également présentés. Enfin, les recommandations concernant la gestion du sang des patients et le traitement de l’anémie sont explorées. La conclusion principale de ce compte rendu souligne que la décision de transfuser des érythrocytes est complexe et dépend de l’interaction de plusieurs facteurs, notamment de l’équilibre entre le risque de l’anémie et le risque de la transfusion d’érythrocytes, les comorbidités existantes du patient, et les risques médicaux et chirurgicaux. Les seuils de transfusion recommandés par les directives actuelles sont différents pour les populations de patients médicaux et chirurgicaux. Les directives proposant des seuils de transfusion spécifiques en fonction des différentes populations de patients devraient être considérées comme point de départ pour prendre une décision informée concernant la transfusion d’érythrocytes. Les alternatives à la transfusion (c.-à-d. la gestion du sang des patients), les biomarqueurs d’une hypoxie tissulaire induite par l’anémie et les alternatives à la transfusion devraient continuer à être évalués dans des ERC d’envergure, avec pour but l’amélioration de la survie sans complication des patients en état critique et périopératoires.

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.