Wen-Cheng Chao

Predictive value of serial measurements of sTREM-1 in the treatment response of patients with community-acquired pneumonia.

BACKGROUND/PURPOSE To evaluate the roles of plasma sTREM-1 (soluble triggering receptor expressed on myeloid cells-1) and C-reactive protein (CRP) in predicting treatment response in patients with community-acquired pneumonia (CAP). METHODS Patients with CAP were enrolled prospectively at a medical center in central Taiwan from September 1, 2004 to July 31, 2005. They were treated according to the guidelines proposed by the American Thoracic Society. Patients were noted as nonresponsive to initial treatment if they had one of the following: persistent fever for more than 3 days, progression on chest radiograph, switching to other antibiotics, or need of mechanical ventilation and/or chest tube drainage. RESULTS Fifty-eight patients (43 males/15 females; mean age, 67 +/- 21 years) with CAP were enrolled. Twelve (12/58, 21%) were nonresponsive. In the response group, CRP was reduced up to 58% from day 1 to day 3 (from 18.8 to 7.8 mg/dL), whereas sTREM-1 was reduced by only 15% (from 32.8 to 28.1 pg/mL). In the nonresponse group, CRP still declined 20% (from 22.2 to 17.7 mg/dL), whereas sTREM-1 was persistently high (from 61.7 to 63.7 pg/mL). Using multivariate logistic regression analysis, both CRP (p = 0.006) and sTREM-1 (p = 0.046) on day 3 predicted treatment response significantly, but CRP on day 3 had stronger statistic power. CONCLUSION Both CRP and sTREM-1 on day 3 could be useful in predicting nonresponsive CAP patients. Differential trends between sTREM-1 and CRP in nonresponsive CAP suggest that sTREM-1 could be an adjuvant biomarker to CRP in predicting CAP patients without response to empiric treatment.

Association between a history of mycobacterial infection and the risk of newly diagnosed Sjögren’s syndrome: A nationwide, population-based case-control study

Objective To address the association between a history of tuberculosis (TB) or nontuberculous mycobacterial (NTM) infection and the risk of newly diagnosed Sjögren’s syndrome (SS). Methods Using a nationwide, population-based, claims dataset, and after excluding those who had rheumatoid arthritis or systemic lupus erythematosus, we identified 5,751 newly diagnosed SS cases during 2007–2012, and compared them to 86,265 non-SS controls matched (1:15) for age, sex, and the year of first SS diagnosis date. The association between the risk of incident SS and a history of mycobacterial infection, including TB and NTM, was quantified by calculating odds ratios (ORs) with 95% confidence intervals (CIs) using conditional logistic regression analysis after adjustment for Charlson comorbidity index (CCI) and bronchiectasis. Results The mean age was 55±14 years, and the proportion of female gender was 87.8% in both newly diagnosed SS cases andnon-SS controls. An association was observed between NTM infection (OR, 11.24; 95% CI, 2.37–53.24) and incident SS, but not between TB infection and incident SS (OR, 1.29; 95% CI, 0.97–1.71) after adjustment for CCI and bronchiectasis. The association between NTM and SS risk was remarkably strong among those aged between 45 and 65 years (OR, 39.24; 95% CI, 3.97–387.75) and those without bronchiectasis (OR, 39.98; 95% CI, 3.83–376.92). Conclusion The study reveals a significant association of newly diagnosed SS with a history NTM infection, especially among individuals aged 40–65 years or those without bronchiectasis.

One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study.

Objective To investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012. Methods We used the 2003–2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008–2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. We used propensity score matching (1:6) for age, sex, and the year of the drug index date to re-select the TNFi group and the non-TNFi controls. After adjusting for potential confounders, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to examine the 1-year TB risk in the TNFi group compared with the non-TNFi controls. Subgroup analyses according to the year of treatment initiation and specific TNFi therapy were conducted to assess the trend of 1-year TB risk in TNFi users from 2008 to 2012. Results This study identified 5,349 TNFi-treated RA patients and 32,064 matched non-TNFi-treated controls. The 1-year incidence rates of TB were 1,513 per 105 years among the TNFi group and 235 per 105 years among the non-TNFi controls (incidence rate ratio, 6.44; 95% CI, 4.69–8.33). After adjusting for age, gender, disease duration, comoridities, history of TB, and concomitant medications, TNFi users had an increased 1-year TB risk (HR, 7.19; 95% CI, 4.18–12.34) compared with the non-TNFi-treated controls. The 1-year TB risk in TNFi users increased from 2008 to 2011 and deceased in 2012 when the Food and Drug Administration in Taiwan announced the Risk Management Plan for patients scheduled to receive TNFi therapy. Conclusion This study showed that the 1-year TB risk in RA patients starting TNFi therapy was significantly higher than that in non-TNFi controls in Taiwan from 2008 to 2012.

Association of day 4 cumulative fluid balance with mortality in critically ill patients with influenza: A multicenter retrospective cohort study in Taiwan

Background Fluid balance is a fundamental management of patients with sepsis, and this study aimed to investigate the impact of cumulative fluid balance on critically ill patients with influenza admitted to an intensive care unit (ICU). Methods This multicenter retrospective cohort study was conducted by the Taiwan Severe Influenza Research Consortium (TSIRC) which includes eight medical centers. Patients with virology-proven influenza infection admitted to ICUs between October 2015 and March 2016 were included for analysis. Results A total of 296 patients were enrolled (mean age: 61.4±15.6 years; 62.8% men), and 92.2% (273/296) of them required mechanical ventilation. In the survivors, the daily fluid balance was positive from day 1 to day 3, and then gradually became negative from day 4 to day 7, whereas daily fluid balance was continuously positive in the non-survivors. Using the cumulative fluid balance from day 1–4 as a cut-off point, we found that a negative cumulative day 1–4 fluid balance was associated with a lower 30-day mortality rate (log-rank test, P = 0.003). To evaluate the impact of shock on this association, we divided the patients into shock and non-shock groups. The positive correlation between negative day 1–4 fluid balance and mortality was significant in the non-shock group (log-rank test, P = 0.008), but not in the shock group (log-rank test, P = 0.396). In a multivariate Cox proportional hazard regression model adjusted for age, sex, cerebrovascular disease, and PaO2/FiO2, day 1–4 fluid balance was independently associated with a higher 30-day mortality rate (aHR 1.088, 95% CI: 1.007–1.174). Conclusions A negative day 1–4 cumulative fluid balance was associated with a lower mortality rate in critically ill patients with influenza. Our findings indicate the critical role of conservative fluid strategy in the management of patients with complicated influenza.

Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with a high risk of osteoporosis and fracture. Interleukin (IL)-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA) titers are inversely associated with bone mineral density (BMD). However, the differential effect of ACPA on bone turnover marker (BTM) and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ) treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP), and C-terminal cross-linking telopeptide of type I collagen (CTX) levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years) receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, p = 0.038). Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, p = 0.008). Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.

Association between periodontitis and the risk of palindromic rheumatism: A nationwide, population-based, case-control study

Objective To estimate the association between a history of periodontitis (PD) and the risk of incident palindromic rheumatism (PR). Methods Using a nationwide, administrative database, this study identified 4,421 newly-diagnosed PR cases from 2007 to 2012 and randomly selected 44,210 non-PR controls matched (1:10) for sex, age and the year of the index date. After adjusting for comorbid diabetes mellitus, we estimated the odds ratios (ORs) with 95% confidence intervals (CIs) using conditional logistic regression analysis to quantify the association between a history of PD and the risk of PR. The influences of the lag time and severity of PD were examined by calculating ORs for subgroups of patients based on the time interval between the last PD-related visit and the index date and PD-related cumulative cost and number of visit. Results This study showed an association between a history of PD and incident PR (OR, 1.51; 95% CI, 1.41–1.61). The association remained significant after variation of PD definitions. The magnitude of the association was greater in those with shorter lag time between the latest date of PD diagnosis and PR index date and those who had a higher number of visits for PD or a greater cumulative cost for PD-related visits. After excluding 569 PR patients who developed rheumatoid arthritis after the index date, we found a consistent time- and dose-dependent association between PD and PR risk. Conclusion This study demonstrated a time- and dose-dependent association between PD exposure and PR risk.

Using Objective Fluid Balance Data to Identify Pulmonary Edema in Subjects With Ventilator-Associated Events

BACKGROUND: A ventilator-associated events (VAEs) algorithm was developed to detect events in mechanically ventilated subjects using objective parameters, and we aimed to use objective data of fluid balance to identify pulmonary edema-associated VAEs. METHODS: This single-center retrospective cohort study was conducted in a medical ICU and enrolled all mechanically ventilated patients between July 2016 and June 2017. Electronic medical records were reviewed to obtain data regarding ventilator-associated conditions (VACs), infection-related ventilator-associated complications (IVACs), possible ventilator-associated pneumonia (VAP), and traditionally defined VAP. RESULTS: Of the 1,158 mechanically ventilated subjects, 85 (7.3%) subjects developed VAEs with a corresponding incidence rate of 7.7 events per 1,000 ventilator days. Among the 85 subjects with VAEs, 52 (61.2%) were classified as IVACs, while 23 (27.1%) had possible VAP. Notably, pulmonary edema was the main etiology (29.0%) for VAEs in the 62 subjects with non-possible VAP VAEs. Compared with those without pulmonary edema, subjects with pulmonary edema had a higher positive fluid balance 2 d before (+1,228 vs +173.5 mL, P = .005) and 1 d before (+1,622 vs +313 mL, P = .002) the diagnosis of VAE. In the multivariate logistic regression analysis (adjusted odds ratio [OR]) adjusted for potential confounders, an older age (adjusted OR 1.072, 95% CI 1.001–1.147), receiving renal replacement therapy (adjusted OR 8.906, 95% CI 1.454–54.558), and a positive cumulative difference between fluid balance 2 d and 1 d before VAE indexing (adjusted OR 1.527 per L positive, 95% CI 1.153–2.023) were independently associated with pulmonary edema in subjects with VAEs. CONCLUSION: These findings provide epidemiological evidence of VAEs in a medical ICU and showed that fluid balance may be used to identify pulmonary edema-associated VAEs. Further studies are warranted to validate and translate these findings into an automated surveillance system for VAEs.

Risk of autoimmune rheumatic diseases in patients with palindromic rheumatism: A nationwide, population-based, cohort study

Objective To estimate the relative risk of autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren’s syndrome (SS), dermatomyositis (DM) and polymyositis (PM), among patients with palindromic rheumatism (PR) compared with non-PR individuals. Methods The study utilized 2003–2013 claims data from the Taiwanese National Health Insurance Research Database. We identified 4,421 cases of PR from 2007 to 2012 and randomly chose 44,210 non-PR individuals who matched (1:10) for age, sex and the year of index date without prior history of RA, SLE, SSc, SS, DM, or PM. After adjusting for age, sex, and the Charlson comorbidity index, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard model to quantify the risk of RA, SLE, SS, DM and PM in PR patients compared with that in matched non-PR individuals. Results Among the 4,421 patients with PR, 569 (12.87%) developed RA, 269 (6.08%) developed SS, 113 (2.56%) developed SLE, 5 (0.11%) developed SSc, 8 (0.18%) developed PM, and 1 (0.02%) developed DM. After adjusting for potential confounders, the patients with PR had an increased risk of RA (HR, 118.76; 95% CI, 89.81–157.04), SS (HR, 59.57; 95% CI, 43.87–80.88), SLE (HR, 51.56; 95% CI, 32.96–80.66) PM (HR, 57.38; 95% CI, 6.90–476.83), and SSc (HR, 13.42; 95% CI, 3.79–47.55) but not of DM (HR, 3.44; 95% CI, 0.34–34.59). Conclusion Patients with PR had an increased risk of developing RA, SS, SLE, PM, and SSc.

Association between a history of periodontitis and the risk of systemic lupus erythematosus in Taiwan: A nationwide, population-based, case-control study

Objective To examine the association between a history of periodontitis (PD) and incident systemic lupus erythematosus (SLE) Methods We used 2003–2012 claims data from the Taiwanese National Health Insurance Database to identify 7,204 incident SLE patients during 2007–2012 as the study group, along with randomly selecting 72,040 non-SLE patients matched (1:10) for age, gender, and first diagnosis date (index date) as the control group. The correlation between PD and SLE risk was estimated using conditional logistic regression analysis, after making adjustments for confounders (including a history of diabetes and number of non-PD related dental visits before the index date). To evaluate the effects of PD severity and the lag time which occurred since the last PD visit on SLE development, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for subgroups of patients with PD according to their number of visits, cumulative cost and also the time gaps between their last PD-related visit and the index date. Results A statistically significant association between a history of PD and newly diagnosed SLE was observed (OR, 1.21; 95% CI, 1.14–1.28; p-value, <0.001). The association was both dose- and time-dependent and was found to be strongest when the interval between the last PD-related visit and the index date was less than three months (OR, 1.83; 95% CI, 1.61–2.09; p-value, <0.001). The association between PD exposure and SLE risk was consistently significant among subgroups stratified based on age, gender, or DM status. Conclusions The results of this nationwide, population-based, case-control study suggest that there is a significant association between a history of PD and incident SLE in Taiwan. This weak association is limited to lack of information on individual smoking status in the database.