Risk Factors for Myocardial Infarction and Stroke Among Sepsis Survivors: A Competing Risks Analysis.

OBJECTIVES: Predictors for post-sepsis myocardial infarction (MI) and stroke are yet to be identified due to the competing risk of death. METHODS: This study included all hospitalized patients with sepsis from National Health Insurance Research Database of Taiwan between 2000 and 2011. The primary outcome was the first occurrence of MI and stroke requiring hospitalization within 180 days following hospital discharge from the index sepsis episode. The association between predictors and post-sepsis MI and stroke were analyzed using cumulative incidence competing risk model that controlled for the competing risk of death. RESULTS: Among 42 316 patients with sepsis, 1012 (2.4%) patients developed MI and stroke within 180 days of hospital discharge. The leading 5 predictors for post-sepsis MI and stroke are prior cerebrovascular diseases (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.74-2.32), intra-abdominal infection (HR: 1.94, 95% CI: 1.71-2.20), previous MI (HR: 1.81, 95% CI: 1.53-2.15), lower respiratory tract infection (HR: 1.62, 95% CI: 1.43-1.85), and septic encephalopathy (HR: 1.61, 95% CI: 1.26-2.06). CONCLUSIONS: Baseline comorbidities and sources of infection were associated with an increased risk of post-sepsis MI and stroke. The identified risk factors may help physicians select a group of patients with sepsis who may benefit from preventive measures, antiplatelet treatment, and other preventive measures for post-sepsis MI and stroke.

Impact of post-sepsis cardiovascular complications on mortality in sepsis survivors: a population-based study.

BACKGROUND: It remains unclear whether sepsis-related cardiovascular complications have an adverse impact on survival independent of pre-existing comorbidities. To investigate the survival impact of post-sepsis cardiovascular complications among sepsis survivors, we conducted a population-based study using the National Health Insurance Database of Taiwan. METHODS: We identified sepsis patients from the National Health Insurance Research Database of Taiwan using ICD-9-CM codes involving infection and organ dysfunction between 2000 and 2011. Post-sepsis incident myocardial infarction (MI) and stroke were ascertained by ICD-9-CM codes and antiplatelet treatment. We constructed a non-sepsis comparison cohort using propensity score matching to ascertain the association between sepsis and cardiovascular complications. Furthermore, we compared the 180-day mortality and 365-day mortality between patients surviving sepsis with or without post-sepsis MI or stroke within 70 days of hospital discharge. We constructed Cox regression models adjusting for pre-existing comorbidities to evaluate the independent survival impact of post-sepsis MI or stroke among sepsis survivors. RESULTS: We identified 42,316 patients hospitalized for sepsis, from which we matched 42,151 patients 1:1 with 42,151 patients hospitalized without sepsis. Compared to patients hospitalized without sepsis, patients hospitalized with sepsis had an increased risk of MI or stroke (adjusted odds ratio 1.72, 95% CI 1.60-1.85). Among 42,316 patients hospitalized for sepsis, 486 (1.15%) patients developed incident stroke and 108 (0.26%) developed incident MI within 70 days of hospital discharge. Compared to sepsis survivors without cardiovascular complications, sepsis survivors with incident MI or stroke had a higher mortality rate at 180 days (11.68% vs. 4.44%, P = 0.003) and at 365 days (16.75% vs. 7.11%, P = 0.005). Adjusting for age, sex, and comorbidities, post-sepsis MI or stroke was independently associated with increased 180-day (adjusted hazard ratio [HR] 2.16, 95% CI 1.69-2.76) and 365-day (adjusted HR 1.90, 95% CI 1.54-2.32) mortality. CONCLUSIONS: Compared to sepsis patients without incident MI or stroke, sepsis patients with incident MI or stroke following hospital discharge had an increased risk of mortality for up to 365 days of follow-up. This increased risk cannot be explained by pre-sepsis comorbidities.

Risk of incident active tuberculosis disease in patients treated with non-steroidal anti-inflammatory drugs: a population-based study.

BACKGROUND: Mycobacterium tuberculosis (TB) is one of the world's most devastating public health threats. Our goal is to evaluate whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) affect the risk of new incident active TB disease. METHODS: We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan's national health insurance research database. Effects of NSAIDs on active TB were estimated by conditional logistic regression and adjusted using a TB-specific disease risk score (DRS). NSAIDs exposures were defined as having a prescription record of NSAIDs ≧ 7 days that ended between 31 and 90 days prior to the index date. RESULTS: A total of 123,419 users of traditional NSAIDs, 16,392 users of cyclooxygenase-2 selective inhibitor (Coxibs), and 4706 incident cases of active TB were identified. Compared with nonusers, use of traditional NSAIDs was associated with an increased risk of TB in the unadjusted analysis ([RR], 1.39; 95% [CI], 1.24 - 1.57 and DRS adjusted analysis ([ARR], 1.30; 95% [CI], 1.15- 1.47). However, use of Coxibs was not associated with a significant increase in the risk of TB after DRS adjustment ([ARR], 1.23; 95% [CI], 0.89 - 1.70). CONCLUSIONS: In this large population-based study, we found that subjects using traditional NSAIDs were associated with increased risk for active TB. We did not find evidence for a causative mechanism between traditional NSAIDs and TB, and more research is required to verify whether the association between traditional NSAIDs and TB is causal, or simply reflects an increased use of anti-inflammatory drugs in the early phases of TB onset.

Does procalcitonin, C-reactive protein, or interleukin-6 test have a role in the diagnosis of severe infection in patients with febrile neutropenia? A systematic review and meta-analysis.

PURPOSE: The study aims to determine the usefulness of procalcitonin (PCT) and other blood markers for identification of bacterial infection among patients with febrile neutropenia (FN). METHODS: The Medline, EMBASE, and Cochrane databases were searched for articles from 1966 to December 2012. We performed a search to identify articles that examined the diagnostic accuracy of PCT in patients with FN. Statistical analyses (fixed- or random-effect models) were conducted to summarize and calculate the sensitivity, specificity, likelihood ratios, and 95 % confidence intervals (CIs). RESULTS: Twenty-seven studies were included (1960 febrile episodes) for PCT analysis, 13 (1712 febrile episodes) for C-reactive protein (CRP) analysis, and five (314 febrile episodes) for interleukin (IL)-6 analysis. Increased PCT levels (odds ratio [OR] 11.5; 95 % CI 7.6 to 17.3), raised CRP levels (3.3; 2.7 to 4.2), and raised IL-6 levels (10.0; 5.5 to 18.0) were significantly associated with bacterial infection. Overall positive likelihood ratio was 5.49 (4.04-7.45) for PCT, 1.82 (1.42-2.33) for CRP, and 3.68 (2.41-5.60) for IL-6. Overall negative likelihood ratio was 0.40 (0.31-0.51) for PCT, 0.40 (0.26-0.61) for CRP, and 0.33 (0.23-0.46) for IL-6. CONCLUSIONS: Of the three potentially useful markers, PCT had the best positive likelihood ratio and can be used to confirm the diagnosis of bacterial infections in patients with FN. Due to unacceptably high negative likelihood ratio, medical decision for stopping antibiotics based on PCT alone in this high-risk population may not be possible.

SHAKF-PU: Sage-Husa Adaptive Kalman Filtering-Based Pedestrian Characteristic Parameter Update Mechanism for Enhancing Step Length Estimation in Pedestrian Dead Reckoning.

Step length estimation (SLE) is the core process for pedestrian dead reckoning (PDR) for indoor positioning. Original SLE requires accurate estimations of pedestrian characteristic parameter (PCP) by the linear update, which may cause large distance errors. To enhance SLE, this paper proposes the Sage-Husa adaptive Kalman filtering-based PCP update (SHAKF-PU) mechanism for enhancing SLE in PDR. SHAKF has the characteristic of predicting the trend of historical data; the estimated PCP is closer to the true value than the linear update. Since different kinds of pedestrians can influence the PCP estimation, adaptive PCP estimation is required. Compared with the classical Kalman filter, SHAKF updates its Q and R parameters in each update period so the estimated PCP can be more accurate than other existing methods. The experimental results show that SHAKF-PU reduces the error by 24.86% compared to the linear update, and thus, the SHAKF-PU enhances the indoor positioning accuracy for PDR.

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.

Role of procalcitonin in the diagnosis of infective endocarditis: a meta-analysis.

BACKGROUND: Infective endocarditis (IE) is a diagnostic challenge. We aimed to systemically summarize the current evidence on the diagnostic value of procalcitonin (PCT) in identifying IE. METHODS: We searched EMBASE, MEDLINE, Cochrane database, and reference lists of relevant articles with no language restrictions through September 2012 and selected studies that reported the diagnostic performance of PCT alone or compare with other biomarkers to diagnose IE. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random effects models. RESULTS: We found 6 qualifying studies that included 1006 episodes of suspected infection with 216 (21.5%) confirmed IE episodes from 5 countries. Bivariate pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios were 64% (95% confidence interval [CI], 52%-74%), 73% (95% CI 58%-84%), 2.35 (95% CI 1.40-3.95), and 0.50 (95% CI 0.35-0.70), respectively. Of the 5 studies examining C-reactive protein (CRP), the pooled sensitivity, specificity, positive likelihood ratios, and negative likelihood ratios were 75% (95% CI 62%-85%), 73% (95% CI 61%-82%), 2.81 (95% CI 1.70-4.65), and 0.34 (95% CI 0.19-0.60), respectively. The global measures of accuracy, area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio (dOR), showed CRP (AUC 0.80, dOR 8.55) may have higher accuracy than PCT (AUC 0.71, dOR 4.67) in diagnosing IE. CONCLUSIONS: Current evidence does not support the routine use of serum PCT or CRP to rule in or rule out IE in patients suspected to have IE.

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.

Diagnostic role of procalcitonin in patients with suspected appendicitis.

BACKGROUND: The aim of this study was to assess the diagnostic value of procalcitonin (PCT) in emergency department (ED) patients with suspected appendicitis. METHODS: A prospective observational study was carried out in the emergency department of a university hospital between July 2007 and June 2008. Adult patients who presented to the ED with clinically suspected appendicitis were enrolled. Each patient underwent serum PCT, C-reactive protein (CRP), and Alvarado score evaluation on admission. The results of these three measurements were analyzed in relation to the final diagnosis determined by histopathological findings or compatible computed tomography findings. RESULTS: Of the 214 study patients, 113 (52.8 %) had a confirmed diagnosis of appendicitis and 58 had complicated appendicitis (phlegmon, perforation, or gangrene). For the diagnosis of appendicitis, the area under the receiving operating characteristic (ROC) curve is 0.74 for Alvarado score, 0.69 for PCT, and 0.61 for CRP. Overall, the Alvarado score has the best discriminative capability among the three tested markers. We adopted two cutoff point approaches to harness both ends of the diagnostic value of a biomarker. PCT levels were significantly higher in patients with complicated appendicitis. For diagnosis of complicated appendicitis, a cutoff value of 0.5 ng/mL had a sensitivity of 29 % and a specificity of 95 %, while a cutoff value of 0.05 ng/ml had a sensitivity of 85 % and a specificity of 30 % in diagnosing complicated appendicitis. For those with a PCT value in the gray zone, clinical findings may play a more important role. CONCLUSION: The study does not support the hypothesis that the PCT test may be useful for screening ED patients for appendicitis. However, determination of the PCT level may be useful for risk assessment of ED patients with suspected complicated appendicitis.

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.

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.

Evaluation of the value of rapid D-dimer test in conjunction with cardiac troponin I test for early risk stratification of myocardial infarction.

We sought to determine the diagnostic value of a D-dimer test for myocardial infarction (MI). The prospective cohort study was carried in the ED of a university hospital. All included patients were tested for D-dimer and cardiac troponin I (cTnI) on ED admission and additional cTnI 6 h later. AMI was retrospectively confirmed by employing the ESC-ACC-AHA-WHF 2007 universal definition. The discriminative value of D-dimer test was assessed by ROC curve analysis. Multivariate analysis was used to identify independent risk factors associated with D-dimer elevation other than MI. A total of 178 patients were included in this study. Median D-dimer levels were significantly higher in MI patients. A D-dimer value greater than 200 ng/ml was significantly associated with MI. When used alone, the test has a high sensitivity of 91.8% but a low specificity of 23.9%. Combined use of cTnI and D-dimer tests raised the sensitivity to 98.4% and helped early triage a subgroup of low risk patients. However, the test had the downside of 58% false positives. High false positives could be partly explained by the high prevalence of underlying hypercoagulable comorbidities. Diabetes mellitus with chronic renal insufficiency was identified as the strongest risk factor associated with D-dimer elevation in patients without MI. D-dimer test alone has a low diagnostic value for MI. Co-existing hypercoagulable conditions may confound the results. Combining cTnI and D-dimer tests enables early identification a low risk group of patients for MI at the cost of high false positives.

Epidemiology of Emergency Department Sepsis: A National Cohort Study Between 2001 and 2012.

The aim of this study is to examine the incidence trend of sepsis over 11 years and compared mortality outcomes among Taiwanese patients with sepsis admitted from emergency department (ED) and non-ED routes. We used a nationwide health insurance database from Taiwan, which comprise of 23 million beneficiaries. Patients with sepsis were identified by ICD-9 CM codes for infection and organ dysfunction from 2001 to 2012. We performed propensity score matching and compared mortality rates between ED-admitted and non ED-admitted patients.During the 11-year study period, we identified 1,256,684 patients with sepsis. 493,397 (29.3%) were admitted through the ED, and 763,287 (70.7%) were admitted directly to the floor. For patients with sepsis, mortality in ED-admitted patients decreased from 27.2% in 2002 to 21.1% in 2012 while that in non-ED admitted patients decreased from 35.3% in 2002 to 30.7% in 2012. Although patients with sepsis admitted through the ED had a higher incidence of organ dysfunction than patients who were directly admitted, they had more favorable outcomes in mortality, length of intensive care unit stay, and hospital stay. After propensity score matching, ED-admitted patients had a 7% lower risk of 90-day mortality (HR, 0.93, 95% CI, 0.89-0.97) compared with directly admitted patients. During the study period, mortality declined faster among ED admitted sepsis patients than directly admitted sepsis patients. Results of this study should be interpreted in light of limitations. Like other administrative database studies, treatment details are not available. Further clinical studies evaluating the treatment and outcome difference between ED and non-ED admitted sepsis patients are warranted.

Risk of gastrointestinal perforation in patients taking oral fluoroquinolone therapy: An analysis of nationally representative cohort.

BACKGROUND: Fluoroquinolone is a commonly prescribed antimicrobial agent, and up to 20% of its users registers adverse gastroenterological symptoms. We aimed to evaluate the association between use of fluoroquinolone and gastrointestinal tract perforation. METHODS: We conducted a nested case-control study on a national health insurance claims database between 1998 and 2011. The use of fluoroquinolones was classified into current (< 60 days), past (61-365 days prior to the index date) and any prior year use of fluoroquinolones. We used the conditional logistic regression model to estimate rate ratios (RRs), adjusting or matching by a disease risk score (DRS). RESULTS: We identified a cohort of 17,510 individuals diagnosed with gastrointestinal perforation and matched them to 1,751,000 controls. Current use of fluoroquinolone was associated with the greatest increase in risk of gastrointestinal perforations after DRS score adjustment (RR, 1.90; 95% CI, 1.62-2.22). The risk of gastrointestinal perforation was attenuated for past (RR, 1.33; 95% CI, 1.20-1.47) and any prior year use (RR, 1.46; 95% CI, 1.34-1.59). To gain insights into whether the observed association can be explained by unmeasured confounder, we compared the risk of gastrointestinal perforation between fluoroquinolone and macrolide. Use of macrolide, an active comparator, was not associated with a significant increased risk of gastrointestinal perforation (RR, 1.11, 95%CI, 0.15-7.99). Sensitivity analysis focusing on perforation requiring in-hospital procedures also demonstrated an increased risk associated with current use. To mitigate selection bias, we have also excluded people who have never used fluoroquinolone before or people with infectious colitis, enteritis or gastroenteritis. In both of the analysis, a higher risk of gastrointestinal perforation was still associated with the use of fluoroquinolone. CONCLUSIONS: We found that use of fluoroquinolones was associated with a non-negligible increased risk of gastrointestinal perforation, and physicians should be aware of this possible association.

Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis: A Population-Based Study.

Numerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB.We conducted a nested case-control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates.From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78-0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66-0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine.In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk.

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.

Risk factors for development of chronic kidney disease following renal infarction: retrospective evaluation of emergency room patients from a single center.

BACKGROUND: Previous studies have analyzed factors associated with renal infarction so that patients can be provided with earlier diagnosis and treatment. However, the factors associated with development of chronic kidney disease (CKD) following renal infarction are unknown. METHODS: We retrospectively reviewed the records of patients with a diagnosis of renal infarction based on enhanced computed tomography. All patients were admitted to a single emergency department in Taiwan from 1999 to 2008. Univariate and multivariate analysis were used to assess the effect of different factors on development of CKD based on estimates of the glomerular filtration rate (eGFR) at admission and at 3-12 months after discharge. RESULTS: Univariate analysis indicated significantly increased risk of CKD in patients older than 50 years, with symptoms for 24 h or less before admission, lower eGFR at admission, APACHE II score greater than 7, SOFA score greater than 1, ASA score greater than 2, and SAPS II score greater than 15. Multivariate analysis indicated that only SOFA score greater than 1 was significantly and independently associated with CKD at follow-up (p<0.001). CONCLUSIONS: A total of 32.5% of patients admitted for renal infarction over a ten-year period developed CKD at 3-12 months after discharge. A SOFA score greater than 1 was significantly and independently associated with development of CKD in these patients.

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.

Can procalcitonin tests aid in identifying bacterial infections associated with influenza pneumonia? A systematic review and meta-analysis.

OBJECTIVE: To summarize evidence for the diagnostic accuracy of procalcitonin (PCT) tests for identifying secondary bacterial infections in patients with influenza. METHODS: Major databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies published between January 1966 and May 2009 that evaluated PCT as a marker for diagnosing bacterial infections in patients with influenza infections and that provided sufficient data to construct two-by-two tables. RESULTS: Six studies were selected that included 137 cases with bacterial coinfection and 381 cases without coinfection. The area under a summary ROC curve was 0·68 (95% CI: 0·64-0·72). The overall sensitivity and specificity estimates for PCT tests were 0·84 (95% CI: 0·75-0·90) and 0·64 (95% CI: 0·58-0·69), respectively. These studies reported heterogeneous sensitivity estimates ranging from 0·74 to 1·0. The positive likelihood ratio for PCT (LR+ = 2·31; 95% CI: 1·93-2·78) was not sufficiently high for its use as a rule-in diagnostic tool, while its negative likelihood ratio was reasonably low for its use as a rule-out diagnostic tool (LR- = 0·26; 95% CI: 0·17-0·40). CONCLUSIONS: Procalcitonin tests have a high sensitivity, particularly for ICU patients, but a low specificity for identifying secondary bacterial infections among patients with influenza. Because of its suboptimal positive likelihood ratio and good negative likelihood ratio, it can be used as a suitable rule-out test but cannot be used as a standalone rule-in test.