Invasive pulmonary aspergillosis among patients with severe community-acquired pneumonia and influenza in ICUs: a retrospective cohort study.

RATIONALE: The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. OBJECTIVES: To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). METHODS: We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. MEASUREMENTS AND MAIN RESULTS: Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. CONCLUSIONS: An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

The impacts of bacterial co-infections and secondary bacterial infections on patients with severe influenza pneumonitis admitted to the intensive care units.

PURPOSES: This study investigated the prevalence and clinical outcomes of pulmonary bacterial co-infections and secondary bacterial infections in patients with severe influenza pneumonitis. METHODS: We retrospectively analyzed the data of adult patients with severe influenza pneumonitis admitted to medical ICUs. Bacterial co-infections and secondary bacterial infections were identified. The risk factors of bacterial infection were evaluated. The outcomes of patients regarding co-infection or secondary bacterial infection were analyzed. RESULTS: We identified 117 critically ill patients with laboratory-confirmed influenza pneumonitis admitted to the medical ICUs. Klebsiella pneumoniae (31.4%) and Staphylococcus aureus (22.8%) were the most identified bacteria in patients with bacterial co-infection. A high proportion of methicillin-resistant Staphylococcus aureus (17.1%) was noted. Liver cirrhosis and diabetes mellitus were the independent risk factors for bacterial co-infection. Acinetobacter baumannii (30.7%) and S. aureus (23.1%) were the most often identified bacteria in patients with secondary bacterial pneumonia. Patients with secondary bacterial infections had a longer duration of mechanical ventilation, and longer ICU and hospital stay. CONCLUSIONS: High rates of drug-resistant bacterial co-infections and secondary bacterial infections were identified in patients with severe influenza pneumonitis requiring ICU care and were associated with more morbidity in these patients.

A highly sensitive and specific real-time quantitative PCR for BRAF V600E/K mutation screening.

Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.

The Risk of Latent Tuberculosis Infection in Respiratory Therapists in a Country with Intermediate Incidence.

BACKGROUND: Respiratory therapists (RTs) are exposed to aerosols more frequently than other health care workers (HCWs) and might bear a higher risk for tuberculosis (TB) infection. The QuantiFERON-TB Gold (QFTG) test was used to evaluate the risk for TB infection in Taiwan, a country with intermediate TB incidence. METHODS: A cross-sectional screening of HCWs, including RTs and other HCWs, with the QFTG test was conducted in Taiwan between October 2008 and December 2011. Those with initially negative QFTG results accepted repeated QFTG testing 1 y later. The positive rates of QFTG in RTs and other HCWs were compared. The risk factors for positive QFTG and QFTG conversion, including occupational group, age, duration of employment, and gender, were analyzed. RESULTS: A total of 274 HCWs were enrolled, including 43 RTs, 163 nurses, and 68 other HCWs. The positive rates of QFTG were 14.0% in RTs, 6.1% in nurses, and 8.8% in other HCWs, which were not significantly different among the 3 groups. Multivariate analysis demonstrated that the risk for positive QFTG positively correlated with increased age and the duration of employment, but did not relate to gender or occupational group. Of 81 HCWs with initially negative QFTG results, 4 (4.9%) had positive conversion on repeat QFTG testing 1 y later. The risk for QFTG conversion in HCWs was not related to occupational group, gender, age, or duration of employment. CONCLUSION: RTs had no higher risk for latent TB infection than other HCWs in a country with intermediate TB incidence.

The clinical outcomes of oldest old patients with tuberculosis treated by regimens containing rifampicin, isoniazid, and pyrazinamide.

OBJECTIVES: To investigate the clinical characteristics, adverse drug reactions, and outcomes of the oldest old patients (aged ≥80 years) with tuberculosis (TB) treated with rifampicin, isoniazid, and pyrazinamide (RIP)-containing regimens. DESIGN: A retrospective chart review study. SETTING: A 1,200-bed tertiary teaching hospital in southwest Taiwan. PARTICIPANTS: We conducted a retrospective observational study between January 1, 2005 and December 31, 2011. Seven hundred adult patients (aged ≥18 years) with TB treated with RIP-containing anti-TB regimens were reviewed, including 161 oldest old patients. OUTCOME MEASURES: Clinical outcomes included clinical responsiveness and microbiological eradication. Adverse outcomes included drug-induced hepatitis, and other symptoms included gastrointestinal upset (eg, abdominal pain, vomiting, diarrhea, or dyspepsia), skin rash, joint pain, and hyperuricemia. RESULTS: Compared with the non-oldest old adult patients, the oldest old patients more frequently had hepatitis (P=0.014), gastrointestinal upset (P=0.029), and unfavorable outcomes (P<0.001). In a multivariate analysis, hepatitis during treatment (adjusted odds ratio: 3.482, 95% confidence interval: 1.537-7.885; P<0.003) and oldest old age (adjusted odds ratio: 5.161, 95% confidence interval: 2.294-11.613; P<0.010) were independent risk factors for unfavorable outcomes. In the oldest old patients with hepatitis, rifampicin use was more common in the favorable outcome group than in the unfavorable outcome group (100% vs 37.5%; P=0.001). CONCLUSION: The oldest old age and hepatitis during RIP treatment were associated with unfavorable outcomes. For the oldest old patients with TB having hepatitis during treatment, rifampicin rechallenge and use might benefit the treatment outcome.

Association between Atmospheric Fine Particulate Matter and Hospital Admissions for Chronic Obstructive Pulmonary Disease in Southwestern Taiwan: A Population-Based Study.

OBJECTIVES: This paper reports on the findings of a population-based study to evaluate the relationship between atmospheric fine particulate matter (PM2.5) levels and hospital admissions for chronic obstructive pulmonary disease (COPD) in southwestern Taiwan over a three-year period, 2008-2010. METHODS: Data on hospital admissions for COPD and PM2.5 levels were obtained from the National Health Insurance Research database (NHIRD) and the Environmental Protection Administration from 2008 to 2010, respectively. The lag structure of relative risks (RRs) of hospital admissions for COPD was estimated using a Poisson regression model. RESULTS: During the study period, the overall average hospitalization rate of COPD and mean 24-h average level of PM2.5 was 0.18% and 39.37 µg/m³, respectively. There were seasonal variations in PM2.5 concentrations in southwestern Taiwan, with higher PM2.5 concentrations in both spring (average: 48.54 µg/m³) and winter (49.96 µg/m³) than in summer (25.89 µg/m³) and autumn (33.37 µg/m³). Increased COPD admissions were significantly associated with PM2.5 in both spring (February-April) and winter (October-January), with the relative risks (RRs) for every 10 µg/m³ increase in PM2.5 being 1.25 (95% CI = 1.22-1.27) and 1.24 (95% CI = 1.23-1.26), respectively, at a lag zero days (i.e., no lag days). Lag effects on COPD admissions were observed for PM2.5, with the elevated RRs beginning at lag zero days and larger RRs estimates tending to occur at longer lags (up to six days, i.e., lag 0-5 days). CONCLUSIONS: In general, findings reveal an association between atmospheric fine particulate matter (PM2.5) and hospital admissions for COPD in southwestern Taiwan, especially during both spring and winter seasons.

Comparison of the efficacy of ciclesonide with that of budesonide in mild to moderate asthma patients after step-down therapy: a randomised parallel-group study.

BACKGROUND: Inhaled corticosteroids (ICSs) are widely used in asthma control. Ciclesonide (CIC) is an ICS with on-site lung activation for potent anti-inflammatory activity. AIMS: This study aimed to compare the clinical benefit of CIC with budesonide (BUD) in step-down therapy. METHODS: A total of 150 patients with mild-to-moderate asthma well controlled by a combination of ICS and long-acting ß2-agonist were randomised to receive either CIC 320 µg (n=75) once daily or 2 inhalations of BUD 200 µg (n=75) twice daily for 12 weeks. The forced expiratory volume in 1s (FEV1), maximum mid-expiratory flow (MMEF) and asthma control test (ACT) scores were measured. Ranked stratification of patients and physicians was assessed. RESULTS: Drug adherence was significantly higher in the CIC group than in the BUD group (76.0% vs. 58.7%, P=0.03). The FEV1 and MMEF remained stable throughout the 12-week CIC treatment. In the BUD group, FEV1 significantly decreased at weeks 4 and 12. MMEF had a higher value in the CIC group than in the BUD group. Both patients and physicians ranked CIC over BUD. CONCLUSIONS: CIC is more effective and has better drug adherence than BUD as step-down treatment when asthma is well controlled by combination therapy.