Bin Du

Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection

BACKGROUNDnDuring the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus.nnnMETHODSnUsing medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013.nnnRESULTSnOf the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02).nnnCONCLUSIONSnDuring the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation

RATIONALEnBaseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear.nnnOBJECTIVESnTo estimate whether mortality in mechanically ventilated patients has changed over time.nnnMETHODSnProspective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models.nnnMEASUREMENTS AND MAIN RESULTSnWe included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92).nnnCONCLUSIONSnPatient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection: risk factors and clinical outcome.

AbstractnObjectives. To study the risk factor for nosocomial bacteremia caused by Escherichiacoli or Klebsiellapneumoniae producing extended-spectrum beta-lactamase (ESBL) and the influence on patient outcome.nDesign. Retrospective, single-center study of consecutive bacteremic patients.nSettings. A university-affiliated teaching hospital.nPatients. A total of 85 patients with nosocomial bacteremia due to E.coli or K.pneumoniae were enrolled.nIntervention. None.nMeasurements and main results. The demographic characteristics and clinical information including treatment were recorded upon review of patients records. The primary end point was hospital mortality. Twenty-seven percent of isolates produced ESBLs. Previous treatment with 3rd-generation cephalosporins was the only independent risk factor for bacteremia due to ESBL-producing pathogens [odds ratio (OR) 4.146, P=0.008]. Antibiotic treatment was considered appropriate in 71 cases (83%), and failed in 23 patients (27%). Twenty-one patients (25%) died in the hospital. Antibiotic treatment failure was the only independent risk factor for hospital mortality (OR 15.376, P=0.001). Inappropriate antibiotic treatment might lead to significantly higher mortality rate (7/14 vs 14/71, P=0.016). Patients treated with imipenem were more likely to survive while those receiving cephalosporin treatment tended to have a poorer outcome (1/19 vs 14/40, P=0.023).nConclusions. More judicious use of cephalosporins, especially 3rd-generation cephalosporins, may decrease ESBL-producing E.coli or K.pneumoniae bacteremia, and also improve patient outcome.

The world's major religions' points of view on end-of-life decisions in the intensive care unit.

ObjectiveRecent research has shown that the religious affiliation of both physicians and patients markedly influences end-of-life decisions in the intensive care unit in the Western world. The worlds major religions standings on withholding and withdrawing of therapy, on hastening of the death process when providing pain relief (double effect) and on euthanasia are described. This review also discusses whether nutrition should be provided to patients in axa0permanent vegetative state, and the issues of brain death and organ donation.DesignThe review is based on literature research and axa0description of the legislature in countries where religious rulings do influence secular law.ResultsNot all religions have distinct rulings on all the above-mentioned issues, but it is pointed out that all religions will probably have to develop rulings on these questions. The importance of patient autonomy in the Western (Christian) world is not necessarily an issue among other ethnic and religious groups, and guidelines are presented with methods to uncover and deal with different ethnic and religious views.ConclusionMany religious groupings are now spread world-wide (most notably Muslims), and with increasing globalization it is important that health-care systems take into account the religious beliefs of axa0wide variety of ethnic and religious groups when contemplating end-of-life decisions.

The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study)

IntroductionDespite evidence demonstrating the value of performance initiatives, marked differences remain between hospitals in the delivery of care for patients with sepsis. The aims of this study were to improve our understanding of how compliance with the 3-h and 6-h Surviving Sepsis Campaign (SSC) bundles are used in different geographic areas, and how this relates to outcome.MethodsThis was a global, prospective, observational, quality improvement study of compliance with the SSC bundles in patients with either severe sepsis or septic shock.ResultsA total of 1794 patients from 62 countries were enrolled in the study with either severe sepsis or septic shock. Overall compliance with all the 3-h bundle metrics was 19xa0%. This was associated with lower hospital mortality than non-compliance (20 vs. 31xa0%, pxa0<xa00.001). Overall compliance with all the 6-h bundle metrics was 36xa0%. This was associated with lower hospital mortality than non-compliance (22 vs. 32xa0%, pxa0<xa00.001). After adjusting the crude mortality differences for ICU admission, sepsis status (severe sepsis or septic shock), location of diagnosis, APACHExa0II score and country, compliance remained independently associated with improvements in hospital mortality for both the 3-h bundle (ORxa0=xa00.64 (95xa0% CI 0.47−0.87), pxa0=xa00.004)) and 6-h bundle (ORxa0=xa00.71 (95xa0% CI 0.56−0.90), pxa0=xa00.005)).DiscussionCompliance with all of the evidence-based bundle metrics was not high. Patients whose care included compliance with all of these metrics had a 40xa0% reduction in the odds of dying in hospital with the 3-h bundle and 36xa0% for the 6-h bundle.

Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study.

Objectives To assess the compliance of Asian intensive care units and hospitals to the Surviving Sepsis Campaign’s resuscitation and management bundles. Secondary objectives were to evaluate the impact of compliance on mortality and the organisational characteristics of hospitals that were associated with higher compliance. Design Prospective cohort study. Setting 150 intensive care units in 16 Asian countries. Participants 1285 adult patients with severe sepsis admitted to these intensive care units in July 2009. The organisational characteristics of participating centres, the patients’ baseline characteristics, the achievement of targets within the resuscitation and management bundles, and outcome data were recorded. Main outcome measure Compliance with the Surviving Sepsis Campaign’s resuscitation (six hours) and management (24 hours) bundles. Results Hospital mortality was 44.5% (572/1285). Compliance rates for the resuscitation and management bundles were 7.6% (98/1285) and 3.5% (45/1285), respectively. On logistic regression analysis, compliance with the following bundle targets independently predicted decreased mortality: blood cultures (achieved in 803/1285; 62.5%, 95% confidence interval 59.8% to 65.1%), broad spectrum antibiotics (achieved in 821/1285; 63.9%, 61.3% to 66.5%), and central venous pressure (achieved in 345/870; 39.7%, 36.4% to 42.9%). High income countries, university hospitals, intensive care units with an accredited fellowship programme, and surgical intensive care units were more likely to be compliant with the resuscitation bundle. Conclusions While mortality from severe sepsis is high, compliance with resuscitation and management bundles is generally poor in much of Asia. As the centres included in this study might not be fully representative, achievement rates reported might overestimate the true degree of compliance with recommended care and should be interpreted with caution. Achievement of targets for blood cultures, antibiotics, and central venous pressure was independently associated with improved survival.

Genomic polymorphism within interleukin-1 family cytokines influences the outcome of septic patients.

ObjectiveTo determine the allele frequencies and genotype distribution of interleukin-1&agr;, interleukin-1&bgr;, and interleukin-1 receptor antagonist gene polymorphism in septic patients. DesignProspective, consecutive entry study of septic patients in a general intensive care unit. SettingA 14-bed general intensive care unit of a university hospital. PatientsSixty patients with diagnosis of sepsis, admitted to the intensive care unit between 1997 and 1999. InterventionsNone. Measurement and Main ResultsThe polymorphic regions within intron 6 of interleukin-1&agr; gene containing variable numbers of a tandem repeat (VNTR) of 46 base pairs, and intron 2 of interleukin-1 receptor antagonist gene containing VNTR of 86 base pairs, were amplified by means of polymerase chain reaction. Alleles A1–4 and RN1–4 were identified according to the size of amplified DNA product. The region containing the AvaI polymorphic site at position −511 of interleukin-1&bgr; gene was amplified by polymerase chain reaction and subsequently digested with AvaI restriction enzyme. The allele frequencies of interleukin-1 receptor antagonist RN2 and genotype RN2/2 were increased in 60 septic patients compared with normal controls (p < .01 and .05, respectively). Allele frequencies or genotype distribution of interleukin-1&agr; VNTR gene polymorphism and interleukin-1&bgr; AvaI polymorphism did not differ between septic patients and normal controls. In addition, genotypes A2/2, B2/2, and RN2/2 were associated with a significantly higher mortality rate (70% to 80%) in septic patients. Patients with any two of the three alleles (i.e., A2, B2, and RN2) suffered from much more severe sepsis (as measured by the Acute Physiology and Chronic Health Evaluation II and Multiple Organ Dysfunction Syndrome score) and a higher mortality rate (55% to 65%), whereas septic patients with genotypes A1/1, B1/1, or RN1/1 showed a much lower mortality rate (0% to 13%). ConclusionsAllele interleukin-1RN2, but not interleukin-1A or interleukin-1B gene polymorphism, was associated with susceptibility to sepsis. Alleles A2, B2, and RN2 might be important high-risk genetic markers for sepsis.

Restriction of third-generation cephalosporin use decreases infection-related mortality.

ObjectiveTo determine the effect of restriction of third-generation cephalosporin use on antibiotic resistance and the outcome of patients with infection. DesignA prospective, before–after comparative study. SettingA general intensive care unit with 14 beds at a university-affiliated teaching hospital. PatientsAll patients admitted to the intensive care unit within 2 yrs. InterventionsA new antibiotic treatment strategy was implemented during phase II. All patients with confirmed or suspected Gram-negative bacterial infections were treated mainly with antibiotics other than third-generation cephalosporins. Measurements and Main ResultsAntibiotic resistance among common Gram-negative bacilli and infection-related hospital mortality during phase I were compared with phase II. A 26.6% reduction in third-generation cephalosporin use (from 168.2 ± 48.0 to 123.5 ± 39.3 g/month, p = .021), accompanied by a 277.7% increase in cefepime use (from 10.3 ± 19.2 to 38.9 ± 31.7 g/month, p = .014) occurred in phase II compared with phase I. This was accompanied by a significant decrease in reduced susceptibility of Gram-negative bacilli to third-generation cephalosporins (p < .05), mainly because of the improved susceptibility of Escherichia coli and Klebsiella species (p < .05). Infection-related hospital mortality was significantly lower in phase II (19.3% vs. 36.3%, p = .014). Multiple logistic regression analysis demonstrated lower respiratory tract infection, the status of immunocompromise, and continuous veno-venous hemofiltration as independent risk factors for infection-related hospital mortality (p < .05), whereas infection with E. coli or Klebsiella species (p = .039) and restriction of third-generation cephalosporin use (p = .025) were associated with a significantly lower mortality rate. ConclusionsRestriction of third-generation cephalosporin use may improve the antibiotic susceptibility and reduce infection-related hospital mortality in critically ill patients.

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome

AbstractPurposeTo analyze the relationship between hypercapnia developing within the first 48xa0h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).nPatients and methodsWe performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12xa0h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.Main outcomesWe included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48xa0h and mortality suggests higher mortality at or above PaCO2 of ≥50xa0mmHg. Patients with severe hypercapnia (PaCO2 ≥50xa0mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; pxa0=xa00.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; pxa0=xa00.032).nConclusionsSevere hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.Trial registrationClinicaltrials.gov identifier, NCT01093482.

Prediction and Outcome of Intensive Care Unit-Acquired Paresis

Background: Intensive care unit-acquired paresis (ICUAP) is associated with poor outcomes. Our objective was to evaluate predictors for ICUAP and the short-term outcomes associated with this condition. Methods: A secondary analysis of a prospective study including 4157 mechanically ventilated adults in 494 intensive care units from 39 countries. After sedative interruption, patients were screened for ICUAP daily, which was defined as the presence of symmetric and flaccid quadriparesis associated with decreased or absent deep tendon reflexes. A multinomial logistic regression was used to create a predictive model for ICUAP. Propensity score matching was used to estimate the relationship between ICUAP and short-term outcomes (ie, weaning failure and intensive care unit [ICU] mortality). Results: Overall, 114 (3%) patients had ICUAP. Variables associated with ICUAP were duration of mechanical ventilation (relative risk ratio [RRR] per day, 1.10; 95% confidence interval [CI] 1.08-1.12), steroid therapy (RRR 1.8; 95% CI, 1.2-2.8), insulin therapy (RRR 1.8; 95% CI 1.2-2.7), sepsis (RRR 1.9; 95% CI: 1.2 to 2.9), acute renal failure (RRR 2.2; 95% CI 1.5-3.3), and hematological failure (RRR 1.9; 95% CI: 1.2-2.9). Coefficients were used to generate a weighted scoring system to predict ICUAP. ICUAP was significantly associated with both weaning failure (paired rate difference of 22.1%; 95% CI 9.8-31.6%) and ICU mortality (paired rate difference 10.5%; 95% CI 0.1-24.0%). Conclusions: Intensive care unit-acquired paresis is relatively uncommon but is significantly associated with weaning failure and ICU mortality. We constructed a weighted scoring system, with good discrimination, to predict ICUAP in mechanically ventilated patients at the time of awakening.