Jan O Friedrich

University of Toronto, Toronto, Ontario, Canada

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Publications (93)508.96 Total impact

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    ABSTRACT: Colchicine has unique anti-inflammatory properties that may be beneficial in various cardiovascular conditions. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines this issue. We searched MEDLINE, EMBASE, and the Cochrane Database from inception to June 2014 for RCTs using colchicine in adult patients with cardiac diseases. Results were pooled using random effects. 15 RCTs (n = 3431 patients, median treatment 3 and follow-up 15 months) were included. All but 2 used colchicine 1 mg/day. In 5 trials, n = 1301) at risk for cardiovascular disease (coronary artery disease, acute coronary syndrome or stroke, post-angioplasty [2 RCTs], or congestive heart failure), colchicine reduced composite cardiovascular outcomes by ~60 % (risk ratio [RR] 0.44, 95 % confidence interval [CI] 0.28-0.69, p = 0.0004; I 2 = 0 %) and showed a trend towards lower all-cause mortality (RR 0.50, 95 % CI 0.23-1.08, p = 0.08; I 2 = 0 %). In pericarditis or post-cardiotomy, colchicine decreased recurrent pericarditis or post-pericardiotomy syndrome (RR 0.50, 95 % CI 0.41-0.60, p < 0.0001; I 2 = 0 %; 8 RCTs, n = 1635), and post-pericardiotomy or ablation induced atrial fibrillation (RR 0.65, 95 % CI 0.51-0.82, p = 0.0003; I 2 = 31 %; 4 RCTs, n = 1118). The most common adverse event was diarrhea. Treatment discontinuation overall and due to adverse events (RR 4.34, 95 % CI 1.70-11.07, p = 0.002; I 2 = 29 %; 7 RCTs, 83/790 [10.5 %] vs. 11/697 [1.6 %]) was higher in colchicine-assigned patients. Current RCT data suggests that colchicine may reduce the composite rate of cardiovascular adverse outcomes in a range of patients with established cardiovascular disease. Furthermore, colchicine reduces rates of recurrent pericarditis, post-pericardiotomy syndrome, and peri-procedural atrial fibrillation following cardiac surgery. Further RCTs evaluating the potential of colchicine for secondary prevention of cardiovascular events would be of interest.
    BMC Cardiovascular Disorders 08/2015; 15(1):96. DOI:10.1186/s12872-015-0068-3 · 1.88 Impact Factor
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    ABSTRACT: Sustained low efficiency dialysis (SLED) is increasingly used as a renal replacement modality in critically ill patients with acute kidney injury (AKI) and hemodynamic instability. SLED may reduce the hemodynamic perturbations of intermittent hemodialysis, while obviating the resource demands of CRRT. Although SLED is being increasingly used, few studies have evaluated its impact on clinical outcomes. We conducted a cohort study comparing SLED (target 8 h/session, blood flow 200 mL/min, predominantly without anticoagulation) to CRRT in four ICUs at an academic medical centre. The primary outcome was mortality 30 days after RRT initiation, adjusted for demographics, comorbidity, baseline kidney function, and Sequential Organ Failure Assessment score. Secondary outcomes were persistent RRT dependence at 30 days and early clinical deterioration, defined as a rise in SOFA score or death 48 h after starting RRT. We identified 158 patients who initiated treatment with CRRT and 74 with SLED. Mortality at 30 days was 54 % and 61 % among SLED- and CRRT-treated patients, respectively [adjusted odds ratio (OR) 1.07, 95 % CI 0.56-2.03, as compared with CRRT]. Among SLED recipients, the risk of RRT dependence at 30 days (adjusted OR 1.36, 95 % CI 0.51-3.57) and early clinical deterioration (adjusted OR 0.73, 95 % CI 0.40-1.34) were not different as compared to patients who initiated CRRT. Notwithstanding the limitations of this small non-randomized study, we found similar clinical outcomes for patients treated with SLED and CRRT. While we await the completion of a trial that will definitively assess the non-inferiority of SLED as compared to CRRT, SLED appears to be an acceptable alternative form of renal support in hemodynamically unstable patients with AKI.
    BMC Nephrology 08/2015; 16(1):127. DOI:10.1186/s12882-015-0123-4 · 1.69 Impact Factor
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    ABSTRACT: In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.Kidney International advance online publication, 8 July 2015; doi:10.1038/ki.2015.184.
    Kidney International 07/2015; 88(4). DOI:10.1038/ki.2015.184 · 8.56 Impact Factor
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    ABSTRACT: Extracorporeal carbon dioxide removal (ECCO2R) has been proposed for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) exacerbations, to avoid intubation or reduce length of invasive ventilation. Balance of risks, efficacy, and benefits of ECCO2R in patients with COPD is unclear. We systematically searched MEDLINE and EMBASE to identify all publications reporting use of ECCO2R in COPD. We looked at physiological and clinical efficacy. A favorable outcome was defined as prevention of intubation or successful extubation. Major and minor complications were compiled. We identified 3123 citations. Ten studies (87 patients), primarily case series, met inclusion criteria. ECCO2R prevented intubation in 65/70 (93 %) patients and assisted in the successful extubation of 9/17 (53 %) mechanically ventilated subjects. One case-control study matching to noninvasively ventilated controls reported lower intubation rates and hospital mortality with ECCO2R that trended toward significance. Physiological data comparing pre- to post-ECCO2R changes suggest improvements for pH (0.07-0.15 higher), PaCO2 (25 mmHg lower), and respiratory rate (7 breaths/min lower), but not PaO2/FiO2. Studies reported 11 major (eight bleeds requiring blood transfusion of 2 units, and three line-related complications, including one death related to retroperitoneal bleeding) and 30 minor complications (13 bleeds, five related to anticoagulation, and nine clotting-related device malfunctions resulting in two emergent intubations). The technique is still experimental and no randomized trial is available. Recognizing selection bias associated with case series, there still appears to be potential for benefit of ECCO2R in patients with COPD exacerbations. However, it is associated with frequent and potentially severe complications. Higher-quality studies are required to better elucidate this risk-benefit balance.
    Intensive Care Medicine 06/2015; 41(10). DOI:10.1007/s00134-015-3921-z · 7.21 Impact Factor
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    Clarence Chant · Norman F. Dewhurst · Jan O. Friedrich
    Intensive Care Medicine 05/2015; 41(7). DOI:10.1007/s00134-015-3718-0 · 7.21 Impact Factor
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    ABSTRACT: Mechanical ventilation is a cornerstone in the management of acute respiratory failure (ARF). Both volume targeted and pressure targeted ventilations are used, the latter modes being increasingly used. We provide a narrative review of the physiological principles of these two types of breath delivery and performed a literature search and analyzed published comparisons between modes. We performed a systematic review and meta-analysis to determine whether pressure control-continuous mandatory ventilation (PC-CMV) or inverse ratio PC-CMV (PC-IRV) has demonstrated advantages over volume control-continuous mandatory ventilation (VC-CMV). The Cochrane tool for risk of bias was used for methodological quality. We also introduced physiological criteria as quality indicators for selecting the studies. Outcomes included compliance, gas exchange, hemodynamics, work of breathing, and clinical outcomes. Analyses were completed with RevMan5 using random effects models. 34 studies met inclusion criteria, many being at high risk of bias. Comparisons of PC-CMV/PC-IRV and VC-CMV did not show any difference for compliance or gas exchange, even when looking at PC-IRV. Calculating the oxygenation index suggested a poorer effect for PC-IRV. There was no difference between modes in terms of hemodynamics, work of breathing, or clinical outcomes. The two modes have different working principles but clinical available data do not suggest any difference in the outcomes. We included all identified trials, enhancing generalizability and attempted to include only sufficient quality physiological studies. However, included trials were small and varied considerably in quality. These data should help to open the choice of ventilation of patients with ARF.
    Chest 04/2015; 148(2). DOI:10.1378/chest.14-3169 · 7.48 Impact Factor
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    ABSTRACT: Shorter resident duty periods are increasingly mandated to improve patient safety and physician well-being. However, increases in continuity-related errors may counteract the purported benefits of reducing fatigue. We evaluated the effects of 3 resident schedules in the intensive care unit (ICU) on patient safety, resident well-being and continuity of care. Residents in 2 university-affiliated ICUs were randomly assigned (in 2-month rotation-blocks from January to June 2009) to in-house overnight schedules of 24, 16 or 12 hours. The primary patient outcome was adverse events. The primary resident outcome was sleepiness, measured by the 7-point Stanford Sleepiness Scale. Secondary outcomes were patient deaths, preventable adverse events, and residents' physical symptoms and burnout. Continuity of care and perceptions of ICU staff were also assessed. We evaluated 47 (96%) of 49 residents, all 971 admissions, 5894 patient-days and 452 staff surveys. We found no effect of schedule (24-, 16- or 12-h shifts) on adverse events (81.3, 76.3 and 78.2 events per 1000 patient-days, respectively; p = 0.7) or on residents' sleepiness in the daytime (mean rating 2.33, 2.61 and 2.30, respectively; p = 0.3) or at night (mean rating 3.06, 2.73 and 2.42, respectively; p = 0.2). Seven of 8 preventable adverse events occurred with the 12-hour schedule (p = 0.1). Mortality rates were similar for the 3 schedules. Residents' somatic symptoms were more severe and more frequent with the 24-hour schedule (p = 0.04); however, burnout was similar across the groups. ICU staff rated residents' knowledge and decision-making worst with the 16-hour schedule. Our findings do not support the purported advantages of shorter duty schedules. They also highlight the trade-offs between residents' symptoms and multiple secondary measures of patient safety. Further delineation of this emerging signal is required before widespread system change. Trial registration: ClinicalTrials.gov, no. NCT00679809. © 8872147 Canada Inc.
    Canadian Medical Association Journal 02/2015; 187(5). DOI:10.1503/cmaj.140752 · 5.96 Impact Factor
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    ABSTRACT: Dialysis-requiring acute kidney injury (AKI) is common among critically ill patients, but little is known about trends in the incidence and outcomes of this condition over time. Population-based cohort study. All adult patients admitted to an intensive care unit in Ontario, Canada, 1996 to 2010. Year and era (1996-2000, 2001-2005, and 2006-2010) of cohort entry. Mortality and dialysis dependence, each evaluated at 90 and 365 days after initiation of dialysis therapy for AKI. The annual incidence proportion of dialysis-requiring AKI was evaluated and patients with this condition were characterized by era. Associations between era and the outcomes of interest were evaluated with Cox proportional hazards (for time to death) and logistic regression (for dialysis dependence), with adjustment for relevant demographic and clinical variables. The annual incidence of dialysis-requiring AKI among critically ill patients increased from 0.8% in 1996 to 3.0% in 2010 (P for trend < 0.001). 90-day mortality declined from 50% in 1996 to 2000 to 45% in 2006 to 2010 (adjusted HR, 0.83 [95% CI, 0.79-0.87] compared to 1996-2000). Dialysis dependence among surviving patients at 90 days was marginally lower in 2006 to 2010 (25.1%) compared to 1996 to 2000 (27.2%), but after adjustment for confounding factors, was not significantly different (adjusted OR, 0.91; 95% CI, 0.80-1.03). Unmeasured confounding by factors that may have changed in patients with dialysis-requiring AKI during the different eras; data set does not allow for mechanistic explanation for the findings; and lack of access to laboratory investigations after hospital discharge. The incidence proportion of dialysis-requiring AKI among critically ill patients increased by almost 4-fold between 1996 and 2010. This was accompanied by a significant decline in mortality, but the risk of long-term dialysis dependence continues to affect a substantial minority of surviving patients with no clear evidence of improvement over time. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 12/2014; 65(6). DOI:10.1053/j.ajkd.2014.10.017 · 5.90 Impact Factor
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    ABSTRACT: To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU. Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial. Sixty-seven medical-surgical ICUs in six countries. Three thousand seven hundred forty-six medical-surgical critically ill patients. All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses. Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03-2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04-1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06-1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02-1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01-3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27-0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27-0.77; p = 0.004). Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such patients.
    Critical Care Medicine 12/2014; 43(2). DOI:10.1097/CCM.0000000000000713 · 6.31 Impact Factor
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    ABSTRACT: Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial.
    Critical Care Medicine 11/2014; 43(2). DOI:10.1097/CCM.0000000000000692 · 6.31 Impact Factor
  • Mark A Bradford · Neill K J Adhikari · Jan O Friedrich
    JAMA The Journal of the American Medical Association 10/2014; 312(15):1588-1589. DOI:10.1001/jama.2014.10780 · 35.29 Impact Factor
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    Critical Care 10/2014; 18(5). DOI:10.1186/s13054-014-0540-y · 4.48 Impact Factor
  • S. Verma · S.G. Goodman · D. Latter · M. Ruel · M.R. Ahsan · M. Gupta · N. Gupta · H. Teoh · J.O. Friedrich
    The Canadian journal of cardiology 10/2014; 30(10):S160. DOI:10.1016/j.cjca.2014.07.242 · 3.71 Impact Factor
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    ABSTRACT: IntroductionPatients with severe acute kidney injury (AKI) who are hospitalized at centres that do not provide renal replacement therapy (RRT) are frequently subjected to inter-hospital transfer for the provision of RRT. It is unclear whether such transfers are associated with worse patient outcomes as compared to the receipt of initial care in a centre that provides RRT. This study examined the relationship between inter-hospital transfer and 30-day mortality among critically ill patients with AKI who received RRT.Methods We conducted a retrospective cohort study of all critically ill patients who commenced RRT for AKI at two academic hospitals in Toronto, Canada. The exposure of interest was inter-hospital transfer for the administration of RRT. We evaluated the relationship between transfer status and 30-day mortality (primary outcome) and RRT dependence at 30 days following RRT initiation (secondary outcome) respectively, using multivariate logistic regression with adjustment for patient demographics, clinical factors, biochemical indices and severity of illness.ResultsOf 370 patients who underwent RRT for AKI, 82 (22.2%) were transferred for this purpose from another hospital. Compared to non-transferred patients who started RRT, transferred patients were younger (61¿±¿15 versus 65¿±¿15 years, P¿=¿0.03) and had a higher serum creatinine concentration at RRT initiation (474¿±¿295 versus 365¿±¿169 ¿mol/L, P¿=¿0.002). Inter-hospital transfer was not associated with mortality (adjusted OR 0.61, 95% CI 0.33 to 1.12) or RRT-dependence (adjusted OR 1.64, 95% CI 0.70 to 3.81) at 30 days.Conclusions Within the limitations of this observational study and the potential for residual confounding, inter-hospital transfer of critically ill patients with AKI was not associated with a higher risk of death or dialysis dependence 30 days after the initiation of acute RRT.
    Critical care (London, England) 09/2014; 18(5):513. DOI:10.1186/PREACCEPT-1084530147129088 · 4.48 Impact Factor
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    ABSTRACT: Automated systems use closed-loop control to enable ventilators to perform basic and advanced functions while supporting respiration. SmartCare™ is a unique automated weaning system that measures selected respiratory variables, adapts ventilator output to individual patient needs by operationalizing predetermined algorithms and automatically conducts spontaneous breathing trials (SBTs) when predetermined thresholds are met.
    Cochrane database of systematic reviews (Online) 09/2014; 9:CD008638. DOI:10.1002/14651858.CD008638.pub2 · 6.03 Impact Factor
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    ABSTRACT: Restrictive red cell transfusion is recommended to minimize risk associated with exposure to allogeneic blood. However, perioperative anemia is an independent risk factor for adverse outcomes after cardiovascular surgery. The purpose of this systematic review and meta-analysis is to determine whether perioperative restrictive transfusion thresholds are associated with inferior clinical outcomes in randomized trials of cardiovascular surgery patients.
    Critical Care Medicine 08/2014; 42(12). DOI:10.1097/CCM.0000000000000548 · 6.31 Impact Factor
  • Critical Care Medicine 08/2014; 42(8):e605-e606. DOI:10.1097/CCM.0000000000000454 · 6.31 Impact Factor
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    ABSTRACT: Background: Mechanical ventilation in the prone position is used to improve oxygenation and to mitigate the harmful effects of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). We sought to determine the effect of prone positioning on mortality among patients with ARDS receiving protective lung ventilation. Methods: We searched electronic databases and conference proceedings to identify relevant randomized controlled trials (RCTs) published through August 2013. We included RCTs that compared prone and supine positioning during mechanical ventilation in patients with ARDS. We assessed risk of bias and obtained data on all-cause mortality (determined at hospital discharge or, if unavailable, after longest follow-up period). We used random-effects models for the pooled analyses. Results: We identified 11 RCTs (n=2341) that met our inclusion criteria. In the 6 trials (n=1016) that used a protective ventilation strategy with reduced tidal volumes, prone positioning significantly reduced mortality (risk ratio 0.74, 95% confidence interval 0.59-0.95; I2=29%) compared with supine positioning. The mortality benefit remained in several sensitivity analyses. The overall quality of evidence was high. The risk of bias was low in all of the trials except one, which was small. Statistical heterogeneity was low (I2<50%) for most of the clinical and physiologic outcomes. Interpretation: Our analysis of high-quality evidence showed that use of the prone position during mechanical ventilation improved survival among patients with ARDS who received protective lung ventilation.
    Canadian Medical Association Journal 05/2014; 186(10). DOI:10.1503/cmaj.140081 · 5.96 Impact Factor
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    ABSTRACT: Controversies regarding the process and timing of the determination of death for controlled organ donation after circulatory death persist. This study assessed the feasibility of conducting a prospective, observational study of continuous monitoring of vital signs for 30 minutes after the clinical determination of death in five Canadian ICUs. Waveform data were analyzed. Prospective observational cohort study. One pediatric and four adult Canadian ICUs. One month of age or older, admitted to the ICU, and for whom a consensual decision to withdraw life-sustaining therapies had been made, with an anticipation of imminent death. None. Invasive arterial blood pressure, electrocardiogram, and oxygen saturation plethysmography activity were recorded and reviewed for 30 minutes after declaration of death. Feasibility was assessed (recruitment, consent rate, protocol compliance, and staff satisfaction). Of 188 subjects screened over 16 months, 41 subjects were enrolled (87% consent rate). Data collection was complete for 30 subjects (73% protocol compliance). In four subjects, arterial blood pressure resumed following cessation of activity. The longest period of cessation of arterial blood pressure before resumption was 89 seconds. The duration of resumed activity ranged from 1 to 172 seconds. No cases of sustained resumption of arterial blood pressure activity were recorded, and no instances of clinical autoresuscitation were reported. In nearly all patients (27 of 30), electrocardiogram activity continued after the disappearance of arterial blood pressure. This is the first observational study to prospectively collect waveform data for 30 minutes after the declaration of death. A future larger study may support initial data suggesting that circulatory function does not resume after more than 89 seconds of absence. Furthermore, persistence of cardiac electrical activity with the documented absence of circulation may not be relevant to declaration of death.
    Critical care medicine 05/2014; 42(11). DOI:10.1097/CCM.0000000000000417 · 6.31 Impact Factor
  • Jan O Friedrich · Andrew J Baker
    Canadian Anaesthetists? Society Journal 05/2014; 61(7). DOI:10.1007/s12630-014-0175-0 · 2.53 Impact Factor

Publication Stats

2k Citations
508.96 Total Impact Points


  • 2001–2014
    • University of Toronto
      • • Department of Medicine
      • • Division of Critical Care Medicine
      • • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2005–2012
    • St. Michael's Hospital
      Toronto, Ontario, Canada
    • Trillium Health Centre
      Mississauga, Ontario, Canada