Background: For patients receiving oral anticoagulant (OAC) therapy, deciding whether to add aspi... more Background: For patients receiving oral anticoagulant (OAC) therapy, deciding whether to add aspirin to their treatment is a common clinical scenario with no clear guidelines to aid practice. We performed a systematic review and meta-analysis of randomized controlled trials comparing these 2 treatment strategies (combined aspirin-OAC therapy vs OAC therapy alone) to assess the therapeutic benefits and risks.
In order to identify molecular changes associated with the transmission of avian influenza A H5N1... more In order to identify molecular changes associated with the transmission of avian influenza A H5N1 and H9N2 viruses to humans, the internal genes from these viruses were compared to sequences from other avian and human influenza A isolates. Phylogenetically, each of the internal genes of all sixteen of the human H5N1 and both of the H9N2 isolates were closely related to one another and fell into a distinct clade separate from clades formed by the same genes of other avian and human viruses. All six internal genes were most closely related to those of avian isolates circulating in Asia, indicating that reassortment with human strains had not occurred for any of these 18 isolates. Amino acids previously identified as host-specific residues were predominantly avian in the human isolates although most of the proteins also contained residues observed previously only in sequences of human influenza viruses. For the majority of the nonglycoprotein genes, three distinct subgroups could be distinguished on bootstrap analyses of the nucleotide sequences, suggesting multiple introductions of avian virus strains capable of infecting humans. The shared nonglycoprotein gene constellations of the human H5N1 and H9N2 isolates and their detection in avian isolates only since 1997 when the first human infections were detected suggest that this particular gene combination may confer the ability to infect humans and cause disease. J. Med. Virol. 66:107–114, 2002. Published 2002 Wiley-Liss, Inc.
Proceedings of The National Academy of Sciences, 2000
In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus res... more In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus resulted in the deaths of six individuals and once again raised the specter of a potentially devastating influenza pandemic. Slaughter of the poultry in the live bird markets removed the source of infection and no further human cases of H5N1 infection have occurred. In March 1999, however, a new pandemic threat appeared when influenza A H9N2 viruses infected two children in Hong Kong. These two virus isolates are similar to an H9N2 virus isolated from a quail in Hong Kong in late 1997. Although differing in their surface hemagglutinin and neuraminidase components, a notable feature of these H9N2 viruses is that the six genes encoding the internal components of the virus are similar to those of the 1997 H5N1 human and avian isolates. This common feature emphasizes the apparent propensity of avian viruses with this genetic complement to infect humans and highlights the potential for the emergence of a novel human pathogen.
Background: The quality of clinical specimens is a crucial determinant for virological diagnosis.... more Background: The quality of clinical specimens is a crucial determinant for virological diagnosis. Objectives: We compared the viral diagnostic yield for influenza A and respiratory syncytial virus (RSV) from the recently developed nasopharyngeal flocked swabs (NPFS) with nasopharyngeal aspirates (NPA) collected in parallel from 196 hospitalized children with acute respiratory infection during the peak period of influenza A and RSV activity in Hong Kong. Specimens were tested by RT-PCR for influenza A and RSV and viral load determined. They were also tested by direct immunofluorescence (DIF) for influenza A and B, RSV, parainfluenza types 1-3 and adenovirus. Results: Both NPA and NPFS had excellent sensitivity (100%) for detecting influenza A by RT-PCR but NPA was slightly more sensitive than NPFS for detecting RSV by both RT-PCR (100% vs. 92.3%) and DIF (87.2% vs. 84.6%) and for detecting influenza A by DIF (90.2% vs. 82.9%). Viral load for influenza A in NPA and NPFS was not significantly different but that for RSV was higher in NPA. Conclusion: NPA remains the optimal specimen for diagnosis of respiratory infections by RT-PCR and DIF. However, collection of NPFS is easier to perform in an out-patient setting, was more acceptable to parents and less likely to generate aerosols than NPA engendering potentially less infection control hazard.
Proceedings of The National Academy of Sciences, 2004
Infection with avian influenza A virus of the H5N1 subtype (isolates A͞HK͞212͞03 and A͞HK͞213͞03)... more Infection with avian influenza A virus of the H5N1 subtype (isolates A͞HK͞212͞03 and A͞HK͞213͞03) was fatal to one of two members of a family in southern China in 2003. This incident was preceded by lethal outbreaks of H5N1 influenza in waterfowl, which are the natural hosts of these viruses and, therefore, normally have asymptomatic infection. The hemagglutinin genes of the A͞HK͞ 212͞03-like viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses that caused the first known cases of human disease in Hong Kong in 1997, but their internal protein genes originated elsewhere. The hemagglutinin of the recent human isolates has undergone significant antigenic drift. Like the 1997 human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of proinflammatory cytokines by primary human macrophages in vitro, whereas the precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The acquisition by the viruses of characteristics that enhance virulence in humans and waterfowl and their potential for wider distribution by infected migrating birds are causes for renewed pandemic concern.
Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and poten... more Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies suggest that antifibrinolytic agents may reduce bleeding and transfusion need in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine if these agents are safe and effective. To address this issue we performed a systematic review of randomized trials describing the use of tranexamic acid, epsilon aminocaproic acid, or aprotinin administration in the perioperative setting. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane databases were searched for relevant trials. Two independent reviewers abstracted total blood loss, transfusion requirements, and venous thromboembolism (VTE) rates. Data were combined using the Mantel-Haenszel method and dichotomous data expressed as relative risk (RR) with 95% confidence intervals (CI). Results: Patients receiving antifibrinolytic agents had reduced transfusion need (RR 0.52; 95% CI, 0.42 to 0.64; P b 0.00001), reduced blood loss and no increase in the risk of VTE (RR 0.95% CI, 0.80 to 1.10, I 2 = 0%, P = 0.531). Conclusions: We conclude that antifibrinolytic agents may reduce bleeding and transfusion in patients undergoing THR or TKA who receive appropriate antithrombotic prophylaxis. There is a need for a large, adequately powered prospective study to carefully examine the safety and efficacy of these agents.
Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated ... more Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality.
The clinical significance of elevated cardiac troponin (cTn) level in patients in the intensive c... more The clinical significance of elevated cardiac troponin (cTn) level in patients in the intensive care unit (ICU) is uncertain. We reviewed the frequency of cTn elevation and its association with mortality and length of ICU stay in these patients.
Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood tra... more Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood transfusions during cardiac surgery, although the effect in children remains unclear. We performed a systematic review of the literature to identify all English language, randomized controlled trials of aprotinin involving children undergoing corrective or palliative cardiac surgery with cardiopulmonary bypass. All studies were assessed for methodological quality, and sources of heterogeneity were examined. We measured the effect of aprotinin on the proportion of children transfused, the volume of blood transfused, and the volume of chest tube drainage. Twelve trials enrolling 626 eligible children met the inclusion criteria. Aprotinin reduced the proportion of children who received red blood cell or whole blood transfusions during cardiac surgery by 33% (relative risk ϭ 0.67; 95% confidence interval, 0.51 to 0.89). Aprotinin did not have a significant effect on the volume of blood transfused or on the amount of postoperative chest tube drainage. Most of the studies were of poor methodological quality and predefined transfusion triggers were infrequently used. Overall, aprotinin reduced the proportion of children who received blood transfusion during cardiac surgery with cardiopulmonary bypass. Further high-quality trials with clinically important outcomes may be warranted before aprotinin can be routinely recommended in this population.
Rituximab, a monoclonal anti-CD20 antibody, is increasingly used to treat idiopathic thrombocytop... more Rituximab, a monoclonal anti-CD20 antibody, is increasingly used to treat idiopathic thrombocytopenic purpura (ITP). To systematically review the literature on the efficacy and safety of rituximab for the treatment of adults with ITP. MEDLINE, EMBASE, the Cochrane Library, abstracts from the American Societies of Hematology and Clinical Oncology annual meetings, and bibliographies of relevant articles and reviews were searched in duplicate until April 2006. Descriptive and comparative studies in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Platelet count response, toxicities, dose, previous treatments, baseline platelet count, duration of ITP, study design, and sources of funding were extracted in duplicate. We identified 19 eligible reports on efficacy (313 patients) and 29 on safety (306 patients). Weighted means for complete response (platelet count > 150 x 10(9) cells/L) and overall response (platelet count > 50 x 10(9) cells/L) with rituximab were 43.6% (95% CI, 29.5% to 57.7%) and 62.5% (CI, 52.6% to 72.5%), respectively. Responses lasted from 2 to 48 months. Nearly all patients had received corticosteroids, and 53.8% had undergone splenectomy. Nine patients (2.9%) died. There were no controlled studies, and no studies met all criteria for study quality. Reported deaths could not necessarily be attributed to rituximab. Overall, the number of rituximab-treated patients with ITP reported in the literature is small. Rituximab resulted in an overall platelet count response in 62.5% of adults with ITP. However, this finding derives from uncontrolled studies that also reported significant toxicities, including death in 2.9% of cases. These data suggest that providers should avoid indiscriminate use of rituximab and that randomized, controlled trials of rituximab for ITP are urgently needed.
Low molecular weight heparin (LMWH) has largely replaced unfractionated heparin (UFH) in patients... more Low molecular weight heparin (LMWH) has largely replaced unfractionated heparin (UFH) in patients with venous thromboembolism because of its pharmacokinetic profile, ease of administration and lack of need for monitoring. The pharmacokinetic profile of LMWH is due to lower molecular weight and reduced charge resulting in less nonspecific protein binding than UFH. These same characteristics make LMWH more dependent on renal function compared with UFH. Consequently, care should be employed when LMWH is administered to patients with impaired renal function as reduced clearance and bioaccumulation may cause bleeding. LMWHs vary in their likelihood of bioaccumulation in chronic renal failure. Enoxaparin bioaccumulates and causes bleeding if administered in therapeutic doses without dose adjustment to patients with impaired renal function. Less rigorous evidence suggests that tinzaparin does not bioaccumulate. Bioaccumulation appears to be greatest in patients with a creatinine clearance less than 30 ml/min, and when therapeutic LMWH doses are used. Care should be used when LMWHs are administered to patients with impaired renal function, particularly those with severe impairment (creatinine clearance below 30 ml/min).
Dose adjustment or laboratory monitoring of low-molecular-weight heparin (LMWH) is commonly recom... more Dose adjustment or laboratory monitoring of low-molecular-weight heparin (LMWH) is commonly recommended for patients with severe renal insufficiency (creatinine clearance < or =30 mL/min), but the basis for this recommendation is unclear. To compare levels of anti-Xa heparin and risk for major bleeding in LMWH-treated patients with a creatinine clearance of 30 mL/min or less versus those with a creatinine clearance greater than 30 mL/min by using standard weight-adjusted therapeutic doses, empirically adjusted doses, or prophylactic doses of LMWH. Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) searched to December 2005 with no language restrictions. The authors also searched reference lists and contacted experts. Observational or subgroups of randomized studies that included non-dialysis-dependent patients with varying degrees of renal function who were treated with LMWH and reported creatinine clearance and anti-Xa levels or major bleeding. Two reviewers independently selected studies and extracted data on patient characteristics, renal function, LMWH treatment, anti-Xa levels, and major bleeding. The pooled odds ratio of major bleeding in patients with a creatinine clearance of 30 mL/min or less was calculated by using the Peto method. Eighteen studies using 3 preparations of LMWH (15 studies using enoxaparin, 2 using tinzaparin, and 1 using dalteparin) were included. Peak anti-Xa levels measured 4 hours after a subcutaneous injection were statistically significantly higher in patients with a creatinine clearance of 30 mL/min or less compared with those with a creatinine clearance greater than 30 mL/min in studies that used a standard therapeutic dose of enoxaparin (4 studies) but not in studies of empirically dose-adjusted enoxaparin (3 studies). Data were insufficient to assess the relationship between anti-Xa and renal function for prophylactic doses of enoxaparin and therapeutic doses of tinzaparin or dalteparin. In 12 studies involving 4971 patients, LMWH was associated with a statistically significant increase in the risk for major bleeding in patients with a creatinine clearance of 30 mL/min or less compared with those with a creatinine clearance greater than 30 mL/min (5.0% vs. 2.4%; odds ratio, 2.25 [95% CI, 1.19 to 4.27]; P = 0.013). When analyzed according to LMWH preparation, major bleeding was increased when a standard therapeutic dose of enoxaparin was used (8.3% vs. 2.4%; odds ratio, 3.88 [CI, 1.78 to 8.45]) but may not be increased when an empirically adjusted dose of enoxaparin is used (0.9% vs. 1.9%; odds ratio, 0.58 [CI, 0.09 to 3.78]; P = 0.23 for heterogeneity). There were insufficient studies to assess the risk for major bleeding with tinzaparin, dalteparin, and prophylactic doses of enoxaparin. The data for tinzaparin and dalteparin were limited. Data are observational, and the potential for confounding cannot be excluded. Non-dialysis-dependent patients with a creatinine clearance of 30 mL/min or less who are treated with standard therapeutic doses of enoxaparin have elevated levels of anti-Xa and an increased risk for major bleeding. Empirical dose adjustment of enoxaparin may reduce the risk for bleeding and merits additional evaluation. No conclusions can be made regarding other LMWHs.
Underutilization of anticoagulant prophylaxis may be due to lack of evidence that prophylaxis pre... more Underutilization of anticoagulant prophylaxis may be due to lack of evidence that prophylaxis prevents clinically important outcomes in hospitalized medical patients at risk for venous thromboembolism. To assess the effects of anticoagulant prophylaxis in reducing clinically important outcomes in hospitalized medical patients. MEDLINE, EMBASE, and Cochrane databases were searched to September 2006 without language restrictions. Randomized trials comparing anticoagulant prophylaxis with no treatment in hospitalized medical patients. Any symptomatic pulmonary embolism (PE), fatal PE, symptomatic deep venous thrombosis, all-cause mortality, and major bleeding. Pooled relative risks and associated 95% CIs were calculated. For treatment effects that were statistically significant, the authors determined the absolute risk reduction and the number needed to treat for benefit (NNT(B)) to prevent an outcome. 9 studies (n = 19 958) were included. During anticoagulant prophylaxis, patients had significant reductions in any PE (relative risk, 0.43 [CI, 0.26 to 0.71]; absolute risk reduction, 0.29%; NNT(B), 345) and fatal PE (relative risk, 0.38 [CI, 0.21 to 0.69]; absolute risk reduction, 0.25%; NNT(B), 400), a nonsignificant reduction in symptomatic deep venous thrombosis (relative risk, 0.47 [CI, 0.22 to 1.00]), and a nonsignificant increase in major bleeding (relative risk, 1.32 [CI, 0.73 to 2.37]). Anticoagulant prophylaxis had no effect on all-cause mortality (relative risk, 0.97 [CI, 0.79 to 1.19]). 2 of 9 included studies were not double-blind. Anticoagulant prophylaxis is effective in preventing symptomatic venous thromboembolism during anticoagulant prophylaxis in at-risk hospitalized medical patients. Additional research is needed to determine the risk for venous thromboembolism in these patients after prophylaxis has been stopped.
Conclusion Systematic screening detected elevated cTn measurements and MI in more patients than w... more Conclusion Systematic screening detected elevated cTn measurements and MI in more patients than were found in routine practice. Elevated cTn was an independent predictor of hospital mortality. Further research is needed to evaluate whether screening and subsequent treatment of these patients reduces mortality.
Introduction Elevated troponin levels indicate myocardial injury but may occur in critically ill ... more Introduction Elevated troponin levels indicate myocardial injury but may occur in critically ill patients without evidence of myocardial ischemia. An elevated troponin alone cannot establish a diagnosis of myocardial infarction (MI), yet the optimal methods for diagnosing MI in the intensive care unit (ICU) are not established. The study objective was to estimate the frequency of MI using troponin T measurements, 12-lead electrocardiograms (ECGs) and echocardiography, and to examine the association of elevated troponin and MI with ICU and hospital mortality and length of stay. Method In this 2-month single centre prospective cohort study, all consecutive patients admitted to our medical-surgical ICU were classified in duplicate by two investigators as having MI or no MI based on troponin, ECGs and echocardiograms obtained during the ICU stay. The diagnosis of MI was based on an adaptation of the joint European Society of Cardiology/American College of Cardiology definition: a typical rise or fall of an elevated troponin measurement, in addition to ischemic symptoms, ischemic ECG changes, a coronary artery intervention, or a new cardiac wall motion abnormality. Results We screened 117 ICU admissions and enrolled 115 predominantly medical patients. Of these, 93 (80.9%) had at least one ECG and one troponin; 44 of these 93 (47.3%) had at least one elevated troponin and 24 (25.8%) had an MI. Patients with MI had significantly higher mortality in the ICU (37.5% versus 17.6%; P = 0.050) and hospital (50.0% versus 22.0%; P = 0.010) than those without MI. After adjusting for Acute Physiology and Chronic Health Evaluation II score and need for inotropes or vasopressors, MI was an independent predictor of hospital mortality (odds ratio 3.22, 95% confidence interval 1.04–9.96). The presence of an elevated troponin (among those patients in whom troponin was measured) was not independently predictive of ICU or hospital mortality. Conclusion In this study, 47% of critically ill patients had an elevated troponin but only 26% of these met criteria for MI. An elevated troponin without ischemic ECG changes was not associated with adverse outcomes; however, MI in the ICU setting was an independent predictor of hospital mortality.
The antiphospholipid antibody syndrome is defined by the presence of antiphospholipid antibodies ... more The antiphospholipid antibody syndrome is defined by the presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapies are the mainstay of treatment to reduce the risk of recurrent thromboembolism that characterizes this condition. Limitations in the laboratory testing for antiphospholipid antibodies and changes in the diagnostic criteria for antiphospholipid antibody syndrome are important to recognize as they will affect the type of patients enrolled in the clinical trials evaluating antiphospholipid antibody syndrome therapies. In this review, we discuss the laboratory testing and diagnostic criteria for antiphospholipid antibody syndrome, and examine the evidence supporting the optimal antithrombotic management of patients with antiphospholipid antibodies. Studies addressing the management of patients with antiphospholipid antibodies and venous thromboembolism, and antiphospholipid antibodies and ischemic stroke, will be critically reviewed. Clinical trials and observational studies have evaluated the optimal type, intensity and duration of anticoagulant therapy in patients with antiphospholipid antibodies. Critical evaluation of these studies is required to assess the generalizability of the results and how these results may be applicable to individual patients.
Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and poten... more Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies suggest that antifibrinolytic agents may reduce bleeding and transfusion need in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine if these agents are safe and effective. To address this issue we performed a systematic review of randomized trials describing the use of tranexamic acid, epsilon aminocaproic acid, or aprotinin administration in the perioperative setting. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane databases were searched for relevant trials. Two independent reviewers abstracted total blood loss, transfusion requirements, and venous thromboembolism (VTE) rates. Data were combined using the Mantel-Haenszel method and dichotomous data expressed as relative risk (RR) with 95% confidence intervals (CI). Results: Patients receiving antifibrinolytic agents had reduced transfusion need (RR 0.52; 95% CI, 0.42 to 0.64; P b 0.00001), reduced blood loss and no increase in the risk of VTE (RR 0.95% CI, 0.80 to 1.10, I 2 = 0%, P = 0.531). Conclusions: We conclude that antifibrinolytic agents may reduce bleeding and transfusion in patients undergoing THR or TKA who receive appropriate antithrombotic prophylaxis. There is a need for a large, adequately powered prospective study to carefully examine the safety and efficacy of these agents.
Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated ... more Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality.
Background: For patients receiving oral anticoagulant (OAC) therapy, deciding whether to add aspi... more Background: For patients receiving oral anticoagulant (OAC) therapy, deciding whether to add aspirin to their treatment is a common clinical scenario with no clear guidelines to aid practice. We performed a systematic review and meta-analysis of randomized controlled trials comparing these 2 treatment strategies (combined aspirin-OAC therapy vs OAC therapy alone) to assess the therapeutic benefits and risks.
In order to identify molecular changes associated with the transmission of avian influenza A H5N1... more In order to identify molecular changes associated with the transmission of avian influenza A H5N1 and H9N2 viruses to humans, the internal genes from these viruses were compared to sequences from other avian and human influenza A isolates. Phylogenetically, each of the internal genes of all sixteen of the human H5N1 and both of the H9N2 isolates were closely related to one another and fell into a distinct clade separate from clades formed by the same genes of other avian and human viruses. All six internal genes were most closely related to those of avian isolates circulating in Asia, indicating that reassortment with human strains had not occurred for any of these 18 isolates. Amino acids previously identified as host-specific residues were predominantly avian in the human isolates although most of the proteins also contained residues observed previously only in sequences of human influenza viruses. For the majority of the nonglycoprotein genes, three distinct subgroups could be distinguished on bootstrap analyses of the nucleotide sequences, suggesting multiple introductions of avian virus strains capable of infecting humans. The shared nonglycoprotein gene constellations of the human H5N1 and H9N2 isolates and their detection in avian isolates only since 1997 when the first human infections were detected suggest that this particular gene combination may confer the ability to infect humans and cause disease. J. Med. Virol. 66:107–114, 2002. Published 2002 Wiley-Liss, Inc.
Proceedings of The National Academy of Sciences, 2000
In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus res... more In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus resulted in the deaths of six individuals and once again raised the specter of a potentially devastating influenza pandemic. Slaughter of the poultry in the live bird markets removed the source of infection and no further human cases of H5N1 infection have occurred. In March 1999, however, a new pandemic threat appeared when influenza A H9N2 viruses infected two children in Hong Kong. These two virus isolates are similar to an H9N2 virus isolated from a quail in Hong Kong in late 1997. Although differing in their surface hemagglutinin and neuraminidase components, a notable feature of these H9N2 viruses is that the six genes encoding the internal components of the virus are similar to those of the 1997 H5N1 human and avian isolates. This common feature emphasizes the apparent propensity of avian viruses with this genetic complement to infect humans and highlights the potential for the emergence of a novel human pathogen.
Background: The quality of clinical specimens is a crucial determinant for virological diagnosis.... more Background: The quality of clinical specimens is a crucial determinant for virological diagnosis. Objectives: We compared the viral diagnostic yield for influenza A and respiratory syncytial virus (RSV) from the recently developed nasopharyngeal flocked swabs (NPFS) with nasopharyngeal aspirates (NPA) collected in parallel from 196 hospitalized children with acute respiratory infection during the peak period of influenza A and RSV activity in Hong Kong. Specimens were tested by RT-PCR for influenza A and RSV and viral load determined. They were also tested by direct immunofluorescence (DIF) for influenza A and B, RSV, parainfluenza types 1-3 and adenovirus. Results: Both NPA and NPFS had excellent sensitivity (100%) for detecting influenza A by RT-PCR but NPA was slightly more sensitive than NPFS for detecting RSV by both RT-PCR (100% vs. 92.3%) and DIF (87.2% vs. 84.6%) and for detecting influenza A by DIF (90.2% vs. 82.9%). Viral load for influenza A in NPA and NPFS was not significantly different but that for RSV was higher in NPA. Conclusion: NPA remains the optimal specimen for diagnosis of respiratory infections by RT-PCR and DIF. However, collection of NPFS is easier to perform in an out-patient setting, was more acceptable to parents and less likely to generate aerosols than NPA engendering potentially less infection control hazard.
Proceedings of The National Academy of Sciences, 2004
Infection with avian influenza A virus of the H5N1 subtype (isolates A͞HK͞212͞03 and A͞HK͞213͞03)... more Infection with avian influenza A virus of the H5N1 subtype (isolates A͞HK͞212͞03 and A͞HK͞213͞03) was fatal to one of two members of a family in southern China in 2003. This incident was preceded by lethal outbreaks of H5N1 influenza in waterfowl, which are the natural hosts of these viruses and, therefore, normally have asymptomatic infection. The hemagglutinin genes of the A͞HK͞ 212͞03-like viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses that caused the first known cases of human disease in Hong Kong in 1997, but their internal protein genes originated elsewhere. The hemagglutinin of the recent human isolates has undergone significant antigenic drift. Like the 1997 human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of proinflammatory cytokines by primary human macrophages in vitro, whereas the precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The acquisition by the viruses of characteristics that enhance virulence in humans and waterfowl and their potential for wider distribution by infected migrating birds are causes for renewed pandemic concern.
Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and poten... more Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies suggest that antifibrinolytic agents may reduce bleeding and transfusion need in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine if these agents are safe and effective. To address this issue we performed a systematic review of randomized trials describing the use of tranexamic acid, epsilon aminocaproic acid, or aprotinin administration in the perioperative setting. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane databases were searched for relevant trials. Two independent reviewers abstracted total blood loss, transfusion requirements, and venous thromboembolism (VTE) rates. Data were combined using the Mantel-Haenszel method and dichotomous data expressed as relative risk (RR) with 95% confidence intervals (CI). Results: Patients receiving antifibrinolytic agents had reduced transfusion need (RR 0.52; 95% CI, 0.42 to 0.64; P b 0.00001), reduced blood loss and no increase in the risk of VTE (RR 0.95% CI, 0.80 to 1.10, I 2 = 0%, P = 0.531). Conclusions: We conclude that antifibrinolytic agents may reduce bleeding and transfusion in patients undergoing THR or TKA who receive appropriate antithrombotic prophylaxis. There is a need for a large, adequately powered prospective study to carefully examine the safety and efficacy of these agents.
Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated ... more Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality.
The clinical significance of elevated cardiac troponin (cTn) level in patients in the intensive c... more The clinical significance of elevated cardiac troponin (cTn) level in patients in the intensive care unit (ICU) is uncertain. We reviewed the frequency of cTn elevation and its association with mortality and length of ICU stay in these patients.
Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood tra... more Aprotinin, a potent antifibrinolytic drug, reduces the proportion of adults who receive blood transfusions during cardiac surgery, although the effect in children remains unclear. We performed a systematic review of the literature to identify all English language, randomized controlled trials of aprotinin involving children undergoing corrective or palliative cardiac surgery with cardiopulmonary bypass. All studies were assessed for methodological quality, and sources of heterogeneity were examined. We measured the effect of aprotinin on the proportion of children transfused, the volume of blood transfused, and the volume of chest tube drainage. Twelve trials enrolling 626 eligible children met the inclusion criteria. Aprotinin reduced the proportion of children who received red blood cell or whole blood transfusions during cardiac surgery by 33% (relative risk ϭ 0.67; 95% confidence interval, 0.51 to 0.89). Aprotinin did not have a significant effect on the volume of blood transfused or on the amount of postoperative chest tube drainage. Most of the studies were of poor methodological quality and predefined transfusion triggers were infrequently used. Overall, aprotinin reduced the proportion of children who received blood transfusion during cardiac surgery with cardiopulmonary bypass. Further high-quality trials with clinically important outcomes may be warranted before aprotinin can be routinely recommended in this population.
Rituximab, a monoclonal anti-CD20 antibody, is increasingly used to treat idiopathic thrombocytop... more Rituximab, a monoclonal anti-CD20 antibody, is increasingly used to treat idiopathic thrombocytopenic purpura (ITP). To systematically review the literature on the efficacy and safety of rituximab for the treatment of adults with ITP. MEDLINE, EMBASE, the Cochrane Library, abstracts from the American Societies of Hematology and Clinical Oncology annual meetings, and bibliographies of relevant articles and reviews were searched in duplicate until April 2006. Descriptive and comparative studies in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Platelet count response, toxicities, dose, previous treatments, baseline platelet count, duration of ITP, study design, and sources of funding were extracted in duplicate. We identified 19 eligible reports on efficacy (313 patients) and 29 on safety (306 patients). Weighted means for complete response (platelet count > 150 x 10(9) cells/L) and overall response (platelet count > 50 x 10(9) cells/L) with rituximab were 43.6% (95% CI, 29.5% to 57.7%) and 62.5% (CI, 52.6% to 72.5%), respectively. Responses lasted from 2 to 48 months. Nearly all patients had received corticosteroids, and 53.8% had undergone splenectomy. Nine patients (2.9%) died. There were no controlled studies, and no studies met all criteria for study quality. Reported deaths could not necessarily be attributed to rituximab. Overall, the number of rituximab-treated patients with ITP reported in the literature is small. Rituximab resulted in an overall platelet count response in 62.5% of adults with ITP. However, this finding derives from uncontrolled studies that also reported significant toxicities, including death in 2.9% of cases. These data suggest that providers should avoid indiscriminate use of rituximab and that randomized, controlled trials of rituximab for ITP are urgently needed.
Low molecular weight heparin (LMWH) has largely replaced unfractionated heparin (UFH) in patients... more Low molecular weight heparin (LMWH) has largely replaced unfractionated heparin (UFH) in patients with venous thromboembolism because of its pharmacokinetic profile, ease of administration and lack of need for monitoring. The pharmacokinetic profile of LMWH is due to lower molecular weight and reduced charge resulting in less nonspecific protein binding than UFH. These same characteristics make LMWH more dependent on renal function compared with UFH. Consequently, care should be employed when LMWH is administered to patients with impaired renal function as reduced clearance and bioaccumulation may cause bleeding. LMWHs vary in their likelihood of bioaccumulation in chronic renal failure. Enoxaparin bioaccumulates and causes bleeding if administered in therapeutic doses without dose adjustment to patients with impaired renal function. Less rigorous evidence suggests that tinzaparin does not bioaccumulate. Bioaccumulation appears to be greatest in patients with a creatinine clearance less than 30 ml/min, and when therapeutic LMWH doses are used. Care should be used when LMWHs are administered to patients with impaired renal function, particularly those with severe impairment (creatinine clearance below 30 ml/min).
Dose adjustment or laboratory monitoring of low-molecular-weight heparin (LMWH) is commonly recom... more Dose adjustment or laboratory monitoring of low-molecular-weight heparin (LMWH) is commonly recommended for patients with severe renal insufficiency (creatinine clearance < or =30 mL/min), but the basis for this recommendation is unclear. To compare levels of anti-Xa heparin and risk for major bleeding in LMWH-treated patients with a creatinine clearance of 30 mL/min or less versus those with a creatinine clearance greater than 30 mL/min by using standard weight-adjusted therapeutic doses, empirically adjusted doses, or prophylactic doses of LMWH. Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) searched to December 2005 with no language restrictions. The authors also searched reference lists and contacted experts. Observational or subgroups of randomized studies that included non-dialysis-dependent patients with varying degrees of renal function who were treated with LMWH and reported creatinine clearance and anti-Xa levels or major bleeding. Two reviewers independently selected studies and extracted data on patient characteristics, renal function, LMWH treatment, anti-Xa levels, and major bleeding. The pooled odds ratio of major bleeding in patients with a creatinine clearance of 30 mL/min or less was calculated by using the Peto method. Eighteen studies using 3 preparations of LMWH (15 studies using enoxaparin, 2 using tinzaparin, and 1 using dalteparin) were included. Peak anti-Xa levels measured 4 hours after a subcutaneous injection were statistically significantly higher in patients with a creatinine clearance of 30 mL/min or less compared with those with a creatinine clearance greater than 30 mL/min in studies that used a standard therapeutic dose of enoxaparin (4 studies) but not in studies of empirically dose-adjusted enoxaparin (3 studies). Data were insufficient to assess the relationship between anti-Xa and renal function for prophylactic doses of enoxaparin and therapeutic doses of tinzaparin or dalteparin. In 12 studies involving 4971 patients, LMWH was associated with a statistically significant increase in the risk for major bleeding in patients with a creatinine clearance of 30 mL/min or less compared with those with a creatinine clearance greater than 30 mL/min (5.0% vs. 2.4%; odds ratio, 2.25 [95% CI, 1.19 to 4.27]; P = 0.013). When analyzed according to LMWH preparation, major bleeding was increased when a standard therapeutic dose of enoxaparin was used (8.3% vs. 2.4%; odds ratio, 3.88 [CI, 1.78 to 8.45]) but may not be increased when an empirically adjusted dose of enoxaparin is used (0.9% vs. 1.9%; odds ratio, 0.58 [CI, 0.09 to 3.78]; P = 0.23 for heterogeneity). There were insufficient studies to assess the risk for major bleeding with tinzaparin, dalteparin, and prophylactic doses of enoxaparin. The data for tinzaparin and dalteparin were limited. Data are observational, and the potential for confounding cannot be excluded. Non-dialysis-dependent patients with a creatinine clearance of 30 mL/min or less who are treated with standard therapeutic doses of enoxaparin have elevated levels of anti-Xa and an increased risk for major bleeding. Empirical dose adjustment of enoxaparin may reduce the risk for bleeding and merits additional evaluation. No conclusions can be made regarding other LMWHs.
Underutilization of anticoagulant prophylaxis may be due to lack of evidence that prophylaxis pre... more Underutilization of anticoagulant prophylaxis may be due to lack of evidence that prophylaxis prevents clinically important outcomes in hospitalized medical patients at risk for venous thromboembolism. To assess the effects of anticoagulant prophylaxis in reducing clinically important outcomes in hospitalized medical patients. MEDLINE, EMBASE, and Cochrane databases were searched to September 2006 without language restrictions. Randomized trials comparing anticoagulant prophylaxis with no treatment in hospitalized medical patients. Any symptomatic pulmonary embolism (PE), fatal PE, symptomatic deep venous thrombosis, all-cause mortality, and major bleeding. Pooled relative risks and associated 95% CIs were calculated. For treatment effects that were statistically significant, the authors determined the absolute risk reduction and the number needed to treat for benefit (NNT(B)) to prevent an outcome. 9 studies (n = 19 958) were included. During anticoagulant prophylaxis, patients had significant reductions in any PE (relative risk, 0.43 [CI, 0.26 to 0.71]; absolute risk reduction, 0.29%; NNT(B), 345) and fatal PE (relative risk, 0.38 [CI, 0.21 to 0.69]; absolute risk reduction, 0.25%; NNT(B), 400), a nonsignificant reduction in symptomatic deep venous thrombosis (relative risk, 0.47 [CI, 0.22 to 1.00]), and a nonsignificant increase in major bleeding (relative risk, 1.32 [CI, 0.73 to 2.37]). Anticoagulant prophylaxis had no effect on all-cause mortality (relative risk, 0.97 [CI, 0.79 to 1.19]). 2 of 9 included studies were not double-blind. Anticoagulant prophylaxis is effective in preventing symptomatic venous thromboembolism during anticoagulant prophylaxis in at-risk hospitalized medical patients. Additional research is needed to determine the risk for venous thromboembolism in these patients after prophylaxis has been stopped.
Conclusion Systematic screening detected elevated cTn measurements and MI in more patients than w... more Conclusion Systematic screening detected elevated cTn measurements and MI in more patients than were found in routine practice. Elevated cTn was an independent predictor of hospital mortality. Further research is needed to evaluate whether screening and subsequent treatment of these patients reduces mortality.
Introduction Elevated troponin levels indicate myocardial injury but may occur in critically ill ... more Introduction Elevated troponin levels indicate myocardial injury but may occur in critically ill patients without evidence of myocardial ischemia. An elevated troponin alone cannot establish a diagnosis of myocardial infarction (MI), yet the optimal methods for diagnosing MI in the intensive care unit (ICU) are not established. The study objective was to estimate the frequency of MI using troponin T measurements, 12-lead electrocardiograms (ECGs) and echocardiography, and to examine the association of elevated troponin and MI with ICU and hospital mortality and length of stay. Method In this 2-month single centre prospective cohort study, all consecutive patients admitted to our medical-surgical ICU were classified in duplicate by two investigators as having MI or no MI based on troponin, ECGs and echocardiograms obtained during the ICU stay. The diagnosis of MI was based on an adaptation of the joint European Society of Cardiology/American College of Cardiology definition: a typical rise or fall of an elevated troponin measurement, in addition to ischemic symptoms, ischemic ECG changes, a coronary artery intervention, or a new cardiac wall motion abnormality. Results We screened 117 ICU admissions and enrolled 115 predominantly medical patients. Of these, 93 (80.9%) had at least one ECG and one troponin; 44 of these 93 (47.3%) had at least one elevated troponin and 24 (25.8%) had an MI. Patients with MI had significantly higher mortality in the ICU (37.5% versus 17.6%; P = 0.050) and hospital (50.0% versus 22.0%; P = 0.010) than those without MI. After adjusting for Acute Physiology and Chronic Health Evaluation II score and need for inotropes or vasopressors, MI was an independent predictor of hospital mortality (odds ratio 3.22, 95% confidence interval 1.04–9.96). The presence of an elevated troponin (among those patients in whom troponin was measured) was not independently predictive of ICU or hospital mortality. Conclusion In this study, 47% of critically ill patients had an elevated troponin but only 26% of these met criteria for MI. An elevated troponin without ischemic ECG changes was not associated with adverse outcomes; however, MI in the ICU setting was an independent predictor of hospital mortality.
The antiphospholipid antibody syndrome is defined by the presence of antiphospholipid antibodies ... more The antiphospholipid antibody syndrome is defined by the presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapies are the mainstay of treatment to reduce the risk of recurrent thromboembolism that characterizes this condition. Limitations in the laboratory testing for antiphospholipid antibodies and changes in the diagnostic criteria for antiphospholipid antibody syndrome are important to recognize as they will affect the type of patients enrolled in the clinical trials evaluating antiphospholipid antibody syndrome therapies. In this review, we discuss the laboratory testing and diagnostic criteria for antiphospholipid antibody syndrome, and examine the evidence supporting the optimal antithrombotic management of patients with antiphospholipid antibodies. Studies addressing the management of patients with antiphospholipid antibodies and venous thromboembolism, and antiphospholipid antibodies and ischemic stroke, will be critically reviewed. Clinical trials and observational studies have evaluated the optimal type, intensity and duration of anticoagulant therapy in patients with antiphospholipid antibodies. Critical evaluation of these studies is required to assess the generalizability of the results and how these results may be applicable to individual patients.
Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and poten... more Background: Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies suggest that antifibrinolytic agents may reduce bleeding and transfusion need in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine if these agents are safe and effective. To address this issue we performed a systematic review of randomized trials describing the use of tranexamic acid, epsilon aminocaproic acid, or aprotinin administration in the perioperative setting. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane databases were searched for relevant trials. Two independent reviewers abstracted total blood loss, transfusion requirements, and venous thromboembolism (VTE) rates. Data were combined using the Mantel-Haenszel method and dichotomous data expressed as relative risk (RR) with 95% confidence intervals (CI). Results: Patients receiving antifibrinolytic agents had reduced transfusion need (RR 0.52; 95% CI, 0.42 to 0.64; P b 0.00001), reduced blood loss and no increase in the risk of VTE (RR 0.95% CI, 0.80 to 1.10, I 2 = 0%, P = 0.531). Conclusions: We conclude that antifibrinolytic agents may reduce bleeding and transfusion in patients undergoing THR or TKA who receive appropriate antithrombotic prophylaxis. There is a need for a large, adequately powered prospective study to carefully examine the safety and efficacy of these agents.
Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated ... more Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality.
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Papers by Wendy Lim