Jiunn-Yih Wu

Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis

The aim was to evaluate the diagnostic value of procalcitonin, C‐reactive protein (CRP) and white blood cell count (WBC) in uncomplicated or complicated appendicitis by means of a systematic review and meta‐analysis.

Comparison of the Test Characteristics of Procalcitonin to C-Reactive Protein and Leukocytosis for the Detection of Serious Bacterial Infections in Children Presenting With Fever Without Source: A Systematic Review and Meta-analysis

STUDY OBJECTIVE We determine the usefulness of the procalcitonin for early identification of young children at risk for severe bacterial infection among those presenting with fever without source. METHODS The design was a systematic review and meta-analysis of diagnostic studies. Data sources were searches of MEDLINE and EMBASE in April 2011. Included were diagnostic studies that evaluated the diagnostic value of procalcitonin alone or compared with other laboratory markers, such as C-reactive protein or leukocyte count, to detect severe bacterial infection in children with fever without source who were aged between 7 days and 36 months. RESULTS Eight studies were included (1,883 patients) for procalcitonin analysis, 6 (1,265 patients) for C-reactive protein analysis, and 7 (1,649 patients) for leukocyte analysis. The markers differed in their ability to predict serious bacterial infection: procalcitonin (odds ratio [OR] 10.6; 95% confidence interval [CI] 6.9 to 16.0), C-reactive protein (OR 9.83; 95% CI 7.05 to 13.7), and leukocytosis (OR 4.26; 95% CI 3.22 to 5.63). The random-effect model was used for procalcitonin analysis because heterogeneity across studies existed. Overall sensitivity was 0.83 (95% CI 0.70 to 0.91) for procalcitonin, 0.74 (95% CI 0.65 to 0.82) for C-reactive protein, and 0.58 (95% CI 0.49 to 0.67) for leukocyte count. Overall specificity was 0.69 (95% CI 0.59 to 0.85) for procalcitonin, 0.76 (95% CI 0.70 to 0.81) for C-reactive protein, and 0.73 (95% CI 0.67 to 0.77) for leukocyte count. CONCLUSION Procalcitonin performs better than leukocyte count and C-reactive protein for detecting serious bacterial infection among children with fever without source. Considering the poor pooled positive likelihood ratio and acceptable pooled negative likelihood ratio, procalcitonin is better for ruling out serious bacterial infection than for ruling it in. Existing studies do not define how best to combine procalcitonin with other clinical information.

Outcome of inadequate empirical antibiotic therapy in emergency department patients with community-onset bloodstream infections

BACKGROUND Studies on the effect of inadequate empirical antibiotic therapy on the outcome of patients with systemic infection have led to inconsistent results. METHODS We analysed data from a comprehensive clinical database collected prospectively in a university hospital between 2008 and 2009. All adult patients who registered in the emergency department (ED) with a bloodstream infection (BSI) were enrolled. Empirical therapy was considered adequate if it included antimicrobials to which the specific isolate displayed in vitro susceptibility and that were administered within 24 h of ED admission. The propensity score (PS) was created by a logistic regression model predicting inadequate empirical therapy. PS-adjusted multivariate analysis was performed by the Cox regression model. The Mortality in Emergency Department Sepsis (MEDS) score was used for the adjustment of residual confounding due to differences in the baseline clinical severity of disease. RESULTS Out of 937 episodes of bacteraemia, 255 (27.2%) patients received inadequate empirical antimicrobial therapy. A crude analysis showed that inadequate antibiotic therapy was associated with higher mortality rates (hazard ratio 1.78, 95% CI 1.30-2.45). PS-adjusted multivariate analyses also showed a significant adverse impact (hazard ratio 1.59, 95% CI 1.14-2.28). The clinical disease severity significantly modified the effect of inadequate antibiotic therapy on survival. The magnitude of the adverse impact of inadequate antibiotic therapy decreased with the increasing severity of sepsis (P=0.009). CONCLUSIONS Inadequate empirical antimicrobial therapy for community-onset BSI was associated with higher 30 day mortality rates. Study populations with different clinical severities may have different results, which may help to partly explain the heterogeneous findings in many similar studies.

Use of serum procalcitonin to detect bacterial infection in patients with autoimmune diseases: A systematic review and meta‐analysis

OBJECTIVE To systematically review evidence of the accuracy of the procalcitonin test for diagnosis of bacterial infection in patients with autoimmune disease. METHODS The major databases Medline, EMBase, and the Cochrane Library were searched for studies published between January 1966 and October 2011 that evaluated procalcitonin, alone or in comparison with other laboratory markers such as C-reactive protein (CRP), as a diagnostic marker for bacterial infection in patients with autoimmune disease and provided sufficient data to permit construction of 2 × 2 tables. RESULTS Nine studies were included in the final meta-analysis. The area under the summary receiver operating characteristic curve values were 0.91 (95% confidence interval [95% CI] 0.88-0.93) for procalcitonin and 0.81 (95% CI 0.78-0.84) for CRP. In general, testing for procalcitonin was highly specific for identifying infectious complications, although it was not as sensitive as testing for CRP. Pooled sensitivity was 0.75 (95% CI 0.63-0.84) for procalcitonin tests and 0.77 (95% CI 0.67-0.85) for CRP tests. Pooled specificity was 0.90 (95% CI 0.85-0.93) for procalcitonin tests and 0.56 (95% CI 0.25-0.83) for CRP tests. The positive likelihood ratio for procalcitonin (7.28 [95% CI 5.10-10.38]) was sufficiently high to qualify procalcitonin testing as a rule-in diagnostic tool, while the negative likelihood ratio (0.28 [95% CI 0.18-0.40]) was not sufficiently low to qualify procalcitonin testing as a reliable rule-out diagnostic tool. CONCLUSION Procalcitonin has higher diagnostic value than CRP for the detection of bacterial sepsis in patients with autoimmune disease, and the test for procalcitonin is more specific than sensitive. A procalcitonin test is not recommended to be used in isolation as a rule-out tool.

Comparison of clinical characteristics and performance of pneumonia severity score and CURB-65 among younger adults, elderly and very old subjects

Background Age-related alterations in the clinical characteristics and performance of severity scoring systems for community-acquired pneumonia (CAP) are unknown. Methods Consecutive patients with CAP presenting to the emergency department were prospectively studied. Patients were classified as younger adults (age 18–64 years), elderly (age 65–84 years) and very old subjects (age ≥85 years). Clinical characteristics, complications, outcomes and validity of the pneumonia severity index (PSI) and CURB-65 categories were compared across these three age categories. Results Analysis involved 348 (35.3%) younger adult patients, 438 (44.3%) elderly patients and 201 (20.0%) very old patients. Compared with younger adults, elderly and very old patients had a higher burden of comorbidities and a higher incidence of CAP-related complications. The 30-day mortality rate was 5.2% in younger adults, 7.1% in elderly patients and 9.5% in very old patients. The area under the ROC curve (AUCs) for PSI were 0.87 (95% CI 0.77 to 0.97), 0.85 (95% CI 0.803 to 0.897) and 0.69 (95% CI 0.597 to 0.787) and the AUCs for CURB-65 were 0.80 (95% CI 0.67 to 0.93), 0.73 (95% CI 0.65 to 0.82) and 0.60 (95% CI 0.47 to 0.73) in the younger adult, elderly and very old patients, respectively. A modified PSI or CURB-65 excluding the age variable increased the AUC in most age categories. There was no significant effect of age on 30-day mortality after adjusting for other PSI or CURB-65 variables. Conclusion Elderly patients with CAP have more atypical clinical manifestations and worse outcomes. The underperformance of the PSI in elderly patients may be due to the inappropriate weight given to the age variable. A modification of the cut-off point for PSI or CURB-65 to define severe pneumonia may improve the score performance in elderly patients.

Diagnostic value of procalcitonin for bacterial infection in elderly patients – a systemic review and meta-analysis

To summarise evidence for the diagnostic accuracy of procalcitonin (PCT) tests for identifying systemic bacterial infections in elderly patients.

Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis

Objective To examine the diagnostic value of serum B-type natriuretic peptide (BNP) in acute Kawasaki disease (KD). Design Systematic review and meta-analysis. Data sources A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE and the Cochrane Library from inception to December 2013. We also performed manual screening of the bibliographies of primary studies and review articles, and contacted authors for additional data. Study eligibility criteria We included all BNP and NT-pro (N-terminal prohormone) BNP assay studies that compared paediatric patients with KD to patients with febrile illness unrelated to KD. We excluded case reports, case series, review articles, editorials, congress abstracts, clinical guidelines and all studies that compared healthy controls. Primary and secondary outcome measures The performance characteristics of BNP were summarised using forest plots, hierarchical summary receiver operating characteristic (ROC) curves and bivariate random effects models. Results We found six eligible studies including 279 cases of patients with KD and 203 febrile controls. Six studies examined NT-proBNP and one examined BNP. In general, NT-proBNP is a specific and moderately sensitive test for identifying KD. The pooled sensitivity was 0.89 (95% CI 0.78 to 0.95) and the pooled specificity was 0.72 (95% CI 0.58 to 0.82). The area under the summary ROC curve was 0.87 (95% CI 0.83 to 0.89). The positive likelihood ratio (LR+ 3.20, 95% CI 2.10 to 4.80) was sufficiently high to be qualified as a rule-in diagnostic tool in the context of high pre-test probability and compatible clinical symptoms. A high degree of heterogeneity was found using the Cochran Q statistic. Conclusions Current evidence suggests that NT-proBNP may be used as a diagnostic tool for KD. NT-proBNP has high diagnostic value for identifying KD in patients with protracted undifferentiated febrile illness. Prospective large cohort studies are needed to help determine best cut-off values and further clarify the role of NT-proBNP in the diagnosis process of KD.

Serum procalcitonin and C-reactive protein levels as markers of bacterial infection in patients with liver cirrhosis: a systematic review and meta-analysis☆ , ☆☆

The diagnostic value of procalcitonin (PCT) for patients with liver cirrhosis is unclear. We searched the PubMed, EMBASE, and Cochrane databases for studies published through December 2013 that evaluated the diagnostic performance of PCT for patients with acute or chronic liver disease with suspected systemic infection. We summarized the test performance characteristics by using forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random effects models. Our search identified 230 citations, of which 10 diagnostic studies that evaluated 1144 patients and 435 bacterial infection episodes (32.1%) were ultimately included for analysis. The bivariate pooled sensitivity estimates were 79% (95% confidence interval [CI]: 64%-89%) for PCT tests and 77% (95% CI: 69%-84%) for C-reactive protein (CRP) tests. Pooled specificity estimates were higher for both PCT and CRP tests (PCT, 89% [95% CI: 82%-94%]; CRP, 85% [95% CI: 76%-90%]). The positive likelihood ratio for PCT (LR+, 7.38, 95% CI: 4.70-11.58) was sufficiently high to qualify PCT as a rule-in diagnostic tool, and the negative likelihood ratio for CRP was sufficiently low to qualify CRP as an acceptable rule-out diagnostic tool (LR- 0.23, 95% CI: 0.13-0.41) in patients with no signs of infection. Available clinical evidence showed that PCT has comparable accuracy to CRP for the diagnosis of systemic infection in patients with liver cirrhosis. Compared with patients with normal liver function, both PCT and CRP tests have acceptable accuracy for diagnosing bacterial infection among patients with liver cirrhosis.

Change in Oxygen Saturation Does Not Predict Acute Mountain Sickness on Jade Mountain

OBJECTIVE The purpose of this trial was to establish whether changes in resting oxygen saturation (Spo(2)) during ascent of Jade Mountain is useful in predicting acute mountain sickness (AMS). AMS-risk factors were also assessed. METHODS A prospective trial was conducted on Jade Mountain, Taiwan from October 18 to October 27, 2008. Resting oxygen saturation (Spo(2)) and heart rate (HR) were measured in subjects at the trail entrance (2610 m), on arrival at Paiyun Lodge (3402 m) on day 1, and at Paiyun Lodge after reaching the summit (3952 m) the next day (day 2). AMS was diagnosed with Lake Louise criteria (AMS score ≥4). A total of 787 subjects were eligible for analysis; 286 (32.2%) met the criteria for AMS. RESULTS Subjects who developed AMS had significantly lower Spo(2) than those who did not at the trail entrance (93.1% ± 2.1% vs 93.5% ± 2.3%; P = .023), on arrival at Paiyun Lodge on day 1 (86.2% ± 4.7% vs 87.6% ± 4.3%; P < .001), and on the return back to the Paiyun Lodge after a summit attempt on day 2 (85.5% ± 3.5% vs 89.6% ± 3.2%; P < .001), respectively. Trekkers with AMS were significantly younger (40.0 vs 43.2 years; P < .001), and had less high altitude (>3000 m) travel in the previous 3 months (29.9% vs 37.1%; P = .004). CONCLUSIONS Subjects with AMS had a lower Spo(2) than those without AMS; however, the differences between the 2 groups were not clinically significant. The results of this study do not support the use of pulse oximetry in predicting AMS on Jade Mountain.

Inflammatory markers in cord blood or maternal serum for early detection of neonatal sepsis—a systemic review and meta-analysis

Objective:To perform a quantitative review of the evidence on the diagnostic value of inflammatory markers in maternal serum or umbilical cord blood for the diagnosis of early-onset neonatal sepsis (EONS).Study Design:We searched multiple databases for studies published through March 2013 that evaluated the diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models.Result:Our search identified 3874 citations, of which 15 studies evaluating 2178 episodes of suspected neonatal infection were included for analysis. IL-6 in cord blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a valid rule-in test. IL-6 in cord blood with a LR− of 0.10 (0.05 to 0.21) and PCT in cord blood with a LR− of 0.20 (0.12–0.37) can be qualified as a useful rule-out test. Either CRP or WBC was inadequate for diagnosis of EONS.Conclusion:For cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool. For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An interventional study may be needed to answer whether the addition of these tests will improve the outcome of patients with EONS.