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.

Serum vascular endothelial growth factor affects tissue fluid accumulation and is associated with deteriorating tissue perfusion and oxygenation in severe sepsis: a prospective observational study.

BACKGROUND: Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels. MATERIAL AND METHODS: New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed. RESULTS: Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50-3092.00] mL/day vs. 1069.00 [722.00-1486.75] mL/day, p < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = - 0.246 and - 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038). CONCLUSIONS: In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.

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.

The Impact of Higher Protein Intake in Patients with Prolonged Mechanical Ventilation.

Prolonged mechanical ventilation (PMV) is associated with poor outcomes and a high economic cost. The association between protein intake and PMV has rarely been investigated in previous studies. This study aimed to investigate the impact of protein intake on weaning from mechanical ventilation. Patients with the PMV (mechanical ventilation ≥6 h/day for ≥21 days) at our hospital between December 2020 and April 2022 were included in this study. Demographic data, nutrition records, laboratory data, weaning conditions, and survival data were retrieved from the patient's electronic medical records. A total of 172 patients were eligible for analysis. The patients were divided into two groups: weaning success (n = 109) and weaning failure (n = 63). Patients with daily protein intake greater than 1.2 g/kg/day had significant shorter median days of ventilator use than those with less daily protein intake (36.5 vs. 114 days, respectively, p < 0.0001). Daily protein intake ≥1.065 g/kg/day (odds ratio: 4.97, p = 0.033), daily protein intake ≥1.2 g/kg/day (odds ratio: 89.07, p = 0.001), improvement of serum albumin (odds ratio: 3.68, p = 0.027), and BMI (odds ratio: 1.235, p = 0.014) were independent predictor for successful weaning. The serum creatinine level in the 4th week remained similar in patients with daily protein intake either >1.065 g/kg/day or >1.2 g/kg/day (p = 0.5219 and p = 0.7796, respectively). Higher protein intake may have benefits in weaning in patients with PMV and had no negative impact on renal function.

Comparing Clinical Outcomes of Tiotropium/Olodaterol, Umeclidinium/Vilanterol, and Indacaterol/Glycopyrronium Fixed-Dose Combination Therapy in Patients with Chronic Obstructive Pulmonary Disease in Taiwan: A Multicenter Cohort Study.

Background: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan. Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics. Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period. Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes.

Oxygen pulse (O2P) is a function of stroke volume and cellular oxygen extraction and O2P curve pattern (O2PCP) can provide continuous measurements of O2P. However, measurements of these two components are difficult during incremental maximum exercise. As cardiac function is evaluated using ejection fraction (EF) according to the guidelines and EF can be obtained using first-pass radionuclide ventriculography, the aim of this study was to investigate associations of O2P%predicted and O2PCP with EF in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) and chronic obstructive pulmonary disease (COPD), and also in normal controls. This was a prospective observational cross-sectional study. Correlations of resting left ventricular EF, dynamic right and left ventricular EFs and outcomes with O2P% and O2PCP across the three participant groups were analyzed. A total of 237 male subjects were screened and 90 were enrolled (27 with HFrEF/HFmrEF, 30 with COPD and 33 normal controls). O2P% and the proportions of the three types of O2PCP were similar across the three groups. O2P% reflected dynamic right and left ventricular EFs in the control and HFrEF/HFmrEF groups, but did not reflect resting left ventricular EF in all participants. O2PCP did not reflect resting or dynamic ventricular EFs in any of the subjects. A decrease in O2PCP was significantly related to nonfatal cardiac events in the HFrEF/HFmrEF group (log rank test, p = 0.01), whereas O2P% and O2PCP did not predict severe acute exacerbations of COPD. The findings of this study may clarify the utility of O2P and O2PCP, and may contribute to the currently used interpretation algorithm and the strategy for managing patients, especially those with HFrEF/HFmrEF. (Trial registration number NCT05189301.).

Outcomes of Herpes Simplex Virus Pneumonitis in Critically Ill Patients.

Critically ill patients, such as those in intensive care units (ICUs), can develop herpes simplex virus (HSV) pneumonitis. Given the high prevalence of acute respiratory distress syndrome (ARDS) and multiple pre-existing conditions among ICU patients with HSV pneumonitis, factors predicting mortality in this patient population require further investigation. In this retrospective study, the bronchoalveolar lavage or sputum samples of ICU patients were cultured or subjected to a polymerase chain reaction for HSV detection. Univariable and multivariable Cox regressions were conducted for mortality outcomes. The length of hospital stay was plotted against mortality on Kaplan-Meier curves. Among the 119 patients with HSV pneumonitis (age: 65.8 ± 14.9 years), the mortality rate was 61.34% (73 deaths). The mortality rate was significantly lower among patients with diabetes mellitus (odds ratio [OR] 0.12, 95% confidence interval [CI]: 0.02-0.49, p = 0.0009) and significantly higher among patients with ARDS (OR: 4.18, 95% CI: 1.05-17.97, p < 0.0001) or high (≥30) Acute Physiology and Chronic Health Evaluation II scores (OR: 1.08, 95% CI: 1.00-1.18, p = 0.02). Not having diabetes mellitus (DM), developing ARDS, and having a high Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independent predictors of mortality among ICU patients with HSV pneumonitis.

Efficacy of portable sleep monitoring device in diagnosing central sleep apnea in patients with congestive heart failure.

Introduction: Central sleep apnea (CSA) is a common and serious comorbidity mainly occurring in patients with heart failure (HF), which tends to be underdiagnosed and has not been widely studied. Overnight polysomnography (PSG) is the gold standard for diagnosing CSA; however, the time and expense of the procedure limit its applicability. Portable monitoring (PM) devices are convenient and easy to use; however, they have not been widely studied as to their effectiveness in detecting CSA in patients with HF. In the current study, we examined the diagnostic value of PM as a screening tool to identify instances of CSA among patients with HF. Methods: A total of 22 patients under stable heart failure conditions with an ejection fraction of <50% were enrolled. All patients underwent PM and overnight PSG within a narrow time frame. The measurements of the apnea-hypopnea index (AHI), hypopnea index (HI), central apnea index (CAI), and obstructive apnea index (OAI) obtained from PSG, automatic scoring, and manual scoring of PM were recorded. The results obtained from PSG and those from PM (automatic and manual scoring) were compared to assess the accuracy of PM. Results: Among the patients, CSA in 11 patients was found by PSG. The AHI measurements performed using manual scoring of PM showed a significant correlation with those performed using PSG (r = 0.69; P = 0.01). Nonetheless, mean AHI measurements showed statistically significant differences between PSG and automatic scoring of PM (40.0 vs. 23.7 events/hour, respectively; P < 0.001), as well as between automatic and manual scoring of PM (23.7 vs. 29.5 events/hour; P < 0.001). Central sleep apnea was detected by PM; however, the results were easily misread as obstructive apnea, particularly in automatic scoring. Conclusion: PM devices could be used to identify instances of central sleep apnea among patients with HF. The results from PM were well-correlated with standard PSG results, and manual scoring was preferable to automated scoring.

The association of aspirin use with overall survival of patients with inoperable non-small cell lung cancer: a retrospective study.

BACKGROUND: Studies have indicated that individuals taking aspirin have a reduced risk of cancers and have also established chemo-preventive benefit of aspirin in colorectal cancer. However, research on the association between aspirin use and the survival in patients with lung cancer has revealed inconsistent results. In this study, we investigated the effect of aspirin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients. METHODS: We identified a cohort of 38,842 patients diagnosed with NSCLC between 2000 and 2012 using the Taiwan's National Health Insurance Research Database and used propensity score matching to reduce possible confounding factors. In total, 9864 patients (4932 matched pairs) were included in the matched cohort. Aspirin exposure was analyzed to identify a possible association with mortality in patients with inoperable NSCLC. Time-dependent Cox regression models were used to calculate the hazard ratios (HRs) and the 95% confidence intervals (95% CIs) that corresponded with aspirin exposure. RESULTS: A total of 4979 patients used aspirin at the time of diagnosis of NSCLC. The median overall survival (OS) of the aspirin users was 1.73 (interquartile range, 0.94-3.53) years compared with the 1.30 (interquartile range, 0.69-2.62) years of the non-aspirin users. The Cox proportional hazard model with the time-dependent covariate revealed that aspirin use was associated with a significantly longer OS (HR: 0.83, 95.0% CI: 0.80-0.86). After controlling the sociodemographic characteristics (age, sex, income, and level of urbanization) and lung cancer treatments by propensity score matching, the aspirin users still had a significantly longer OS than the non-aspirin users (HR: 0.79, 95.0% CI: 0.75-0.83). CONCLUSION: Aspirin use is associated with a longer OS in patients with inoperable NSCLC, suggesting that aspirin has a potential anticancer effect. These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients.

Total Sleep Time in the Taiwan Obstructive Lung Disease Cohort.

Patients with chronic obstructive pulmonary disease (COPD) have been reported to have poor sleep quality. However, total sleep time has not been evaluated in detail among patients with COPD. This retrospective, observational, multicenter research study was performed across six participating hospitals in Taiwan, with a total of 421 adult patients enrolled. Pulmonary function, the Modified British Medical Research Council Dyspnea Scale, the COPD Assessment Test and basic clinical data were assessed. The Pittsburgh Sleep Quality Index was also administered to patients, and the total sleep time was extracted for further analysis. The patients whose total sleep time was between 6 and 7 h had better pulmonary function, and the patients who slept less than 5 h had worse comorbidities. There was a significant higher total sleep time in Global Initiatives for Chronic Obstructive Lung Disease (GOLD) group B compared to GOLD group A. COPD patients who sleep between 5 and 6 h used fewer oral steroids and were less likely to use triple therapy (long-acting beta-agonist, long-acting muscarinic antagonist, inhaled cortical steroid). COPD patients sleeping from 5 to 7 h had better clinical features than those sleeping less than 5 h in terms of pulmonary function, comorbidities and medication usage.

Incidence of nontuberculous mycobacterial disease and coinfection with tuberculosis in a tuberculosis-endemic region: A population-based retrospective cohort study.

ABSTRACT: Nontuberculous mycobacteria (NTM) infection may interfere in the diagnosis and treatment of tuberculosis (TB) in TB-endemic regions. However, the population-based incidence of NTM disease and NTM-TB coinfection remains unclear.We used Taiwan's National Health Insurance Research Database to identify new diagnoses of NTM disease and TB from 2005 to 2013 and calculated the incidence rate and the proportion of NTM-TB coinfection. The patients with NTM disease or TB were determined by the use of disease codes from International Classification of Diseases, Ninth Revision, Clinical Modification, laboratory mycobacterium examination codes, and antimycobacterial therapy receipts.From 2005 to 2013, the age-adjusted incidence rate of NTM disease increased from 5.3 to 14.8 per 100,000 people per year and the age-adjusted incidence rate of NTM-TB coinfection was around 1.2 to 2.2 per 100,000 people per year. The proportion of NTM-TB coinfection among patients with confirmed TB was 2.8%. Male and older patients had a significantly higher incidence of NTM disease. The effects of urbanization and socioeconomic status (SES) on the incidences of TB and NTM disease were different. Rural living and lower SES were significantly associated with increasing the incidence of confirmed TB but not with that of NTM disease. For NTM disease, those living in the least urbanized area had significantly lower incidence rate ratio than in the highest urbanized area. The incidence of NTM-TB coinfection was higher in older patients and compared with patients aged < 45 years, the incidence rate ratio of the patients aged> 74 years was 12.5.In TB-endemic Taiwan, the incidence of NTM disease increased from 2005 to 2013. Male gender and old age were risk factors for high incidence of NTM disease. SES did not have a significant effect on the incidence of NTM disease, but rural living was associated with lower incidence of NTM disease. In TB-endemic areas, NTM-TB coinfection could disturb the diagnosis of TB and treatment, especially in elderly 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.

Low Concentrations of Dehydroepiandrosterone Sulfate are Associated with Depression and Fatigue in Patients with Non-Small-Cell Lung Cancer After Chemotherapy.

BACKGROUND: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) concentrations were reported to decrease in patients with advanced cancer. However, the clinical significance of DHEA and DHEAS concentrations in patients with NSCLC receiving chemotherapy (CT) has not been sufficiently documented. OBJECTIVE: To evaluate the correlation between mental health and hormone concentrations on patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The present study was a cross-sectional analysis based on a self-reported psychological investigation. Salivary samples were collected from 22 patients with advanced NSCLC after CT and 17 healthy controls. The concentrations of DHEA, DHEAS, and cortisol were analyzed to investigate their associations with the results of self-reported questionnaires on psychological health. RESULTS: Patients with advanced NSCLC exhibited significantly higher Patient Health Questionnaire (PHQ-9) and Startle, Physiological arousal, Anger, and Numbness-Chinese version (SPAN-C) scores, poorer health conditions, lower sleep quality, and more severe fatigue after CT than did healthy controls, and salivary concentrations of DHEA and DHEAS were significantly lower among patients after CT than among controls. DHEAS concentrations were negatively associated with depression scores (PHQ-9, r = -0.496, P = 0.019) and fatigue scores (Brief Fatigue Inventory-Taiwan, r = -0.562, P = 0.006). CONCLUSION: Patients with advanced NSCLC after CT had lower DHEA and DHEAS concentrations than did controls. Lower DHEAS concentrations were associated with higher fatigue and depression scores.

Effect of high flow nasal cannula on peripheral muscle oxygenation and hemodynamic during paddling exercise in patients with chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND: Exercise training for patients with chronic obstructive pulmonary disease (COPD) improves their endurance and oxygenation. Supplemental oxygen delivered by high flow nasal cannula (HFNC) reportedly improves the clinical outcomes during high-intensity exercise. However, the physical benefits of the provision of supplemental oxygen with HFNC for the improvement of exercise performance have not been fully investigated. This randomized trial aimed to evaluate the effect of HFNC on the hemodynamic status and peripheral muscle microcirculation during exercise training. METHODS: In this multicenter, randomized controlled parallel two-group study, 32 patients with moderate to severe COPD were randomly assigned into the nasal cannula (NC) group (n=15) with a flow rate of 2-3 L/min or the HFNC group (n=17) with a flow rate of 45 L/min for twelve 40 min exercise training sessions. RESULTS: The mean cardiac index (CI) and stroke volume (SV) of the NC group in the first session were significantly lower than those of the HFNC group (3.68±0.76 vs. 4.5±0.76 L/min/m2, P=0.014; 63.03±9.87 vs. 74.22±19.48, P=0.002, respectively). The systemic vascular resistance (SVR) of the NC group was significantly lower in the seventh session than in the first session (891±287 vs. 1,138±381 dyn-s/cm5, respectively, P=0.048). The mean deoxyhemoglobin level was higher in the HFNC group in the 1st session and lower in the 12th session (1.09±9.04 vs. 7.3±7.3 µm, P=0.046). The COPD Assessment Test score, Modified Medical Research Council scale score, maximum inspiratory pressure (MIP), and maximum expiratory pressure were different within and between the groups. CONCLUSIONS: HFNC, with a lower oxygen concentration than that used with a traditional NC, yielded lower deoxygenated hemoglobin levels after 12 suboptimal exercise training sessions. In contrast, the higher oxygen concentration delivered by NC reduced SVR. The COPD assessment score improved on exercise training, regardless of the supplemental oxygen delivery method.

Statin Use and the Risk of Subsequent Hospitalized Exacerbations in COPD Patients with Frequent Exacerbations.

Rationale: The potential benefits of statins for the prevention of exacerbations in patients with COPD remains controversial. No previous studies have investigated the impact of statins on clinical outcomes in COPD patients with frequent exacerbations. Objective: This study aimed to evaluate the association between the use of statins and the risk of subsequent hospitalized exacerbations in COPD frequent exacerbators. Materials and Methods: We conducted a population-based cohort study using the Taiwan National Health Insurance Research Database. 139,223 COPD patients with a first hospitalized exacerbation between 2004 and 2012 were analyzed. Among them, 35,482 had a second hospitalized exacerbation within a year after the first exacerbation, and were defined as frequent exacerbators. 1:4 propensity score matching was used to create matched samples of statin users and non-users. The competing risk regression analysis model was used to evaluate the association between statin use and exacerbation risk. Results: The use of statins was associated with a significantly reduced risk in subsequent hospitalized exacerbations in COPD patients after their first hospitalized exacerbation (adjusted subdistribution hazard ration [SHR], 0.89; 95% CI, 0.85-0.93, P<0.001). In frequent exacerbators, the SHR for subsequent hospitalized exacerbations in statins users was 0.88 (95% CI, 0.81-0.94, P=0.001). Subgroup analysis among frequent exacerbators demonstrated that the use of statins only provided a protective effect against subsequent hospitalized exacerbations in male patients aged 75 years and older, with coexisting diabetes mellitus, hypertension or cardiovascular disease, and no protective effect was observed in those with lung cancer or depression. Current use of statins was associated with a greater protective effect for reducing subsequent hospitalized exacerbation. Conclusion: The use of statins was associated with a significant reduction in the risk of hospitalized exacerbations in COPD patients after a first hospitalized exacerbation and in specified COPD frequent exacerbators.

Improved appropriateness of anti-tuberculosis prescription by the expert prescription review program in Taiwan.

BACKGROUND: A nationwide program initiated by Taiwan CDC was conducted by the Taiwan Society of Tuberculosis and Lung Disease to improve the appropriateness of anti-TB prescriptions in Taiwan. METHODS: All anti-TB prescriptions from 12 hospitals across Taiwan were reviewed by experienced pulmonologists, according to the 2011 Taiwan TB treatment guidelines, between May and October 2013. The investigation period was divided into three stages: May to June, July to August, and September to October. The concordance rates between anti-TB prescriptions and the guidelines were compared among the three stages and between medical centers and regional hospitals. RESULTS: A total of 2574 new anti-TB prescriptions were reviewed. The appropriateness of anti-TB prescriptions was 82.0%. The most dominant error was inappropriate dosage of anti-TB medications. The appropriateness improved significantly with prescription review, and the concordance rates were 78.7%, 80.6%, and 87.6% in stages 1, 2, and 3, respectively (P < 0.001). The inappropriateness of medication dosage also improved significantly, with the rates of inappropriate dosage dropping from 10.2% in stage 1-5.4% in stage 3 (Odds ratio 0.491, P < 0.001). The appropriateness rates showed no significant difference between regional hospitals and medical centers (82.5% vs. 81.3%, Odds ratio 0.915, P = 0.393), but the improvement of prescription appropriateness was significant in regional hospitals but not in medical centers. CONCLUSION: Prescription review by TB experts is an effective approach to improve the appropriateness of anti-TB prescriptions.

Outcomes of severe H1N1 pneumoniae: A retrospective study at intensive care units.

BACKGROUND: The incidence of acute respiratory distress syndrome (ARDS) and the mortality rate of H1N1 influenza pneumonia are unclear. The aim of this study is to investigate the clinical features and outcomes of adult patients admitted to intensive care units (ICUs) with H1N1 pneumonia related ARDS. METHODS: This retrospective study included patients with confirmed H1N1 influenza pneumonia admitted to the ICUs of a medical center between July 2009 and May 2014. We investigated the patients' characteristics, clinical presentations, illness severities, and outcomes. RESULTS: Sixty-six patients were confirmed to have H1N1 influenza pneumonia requiring mechanical ventilation. Fifty-four of those patients (82%) developed ARDS, while their hospital mortality rate was 33% (22/66). There were no significant differences in the ICU and hospital mortality rates of the ARDS and non-ARDS patients. Among the ARDS patients, there were higher rates of solid malignant disease (22.8% vs. 2.8%, p = 0.038) and sepsis (66.7% vs. 33.3%, p = 0.020) and a higher mean tidal volume (8.9 ± 1.8 vs. 7.8 ± 1.9 ml/kg, p = 0.032) in the non-survivors than the survivors. Logistic regression analysis revealed that a high tidal volume (odds ratio = 1.448, 95 % CI = 1.033-2.030; p = 0.032) and sequential organ failure assessment (SOFA) score (odds ratio = 1.233, 95% CI = 1.029-1.478; p = 0.023) were the risk factors of hospital mortality. CONCLUSION: For H1N1 influenza pneumonia patients admitted to ICUs with mechanical ventilation, there is a high probability of developing ARDS with a modest mortality rate. For patients with ARDS due to H1N1 influenza pneumonia, the tidal volume and SOFA score are the predictors of hospital mortality.

Concurrent proton-pump inhibitors increase risk of death for lung cancer patients receiving 1st-line gefitinib treatment - a nationwide population-based study.

PURPOSE: Concurrent proton pump inhibitor (PPI) use might reduce the plasma concentration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Clinically, the adverse effect of PPIs on patients with non-small cell lung cancer (NSCLC) treated with first-line EGFR TKIs remains controversial. This study was conducted to evaluate whether the combined use of gefitinib with PPIs affected NSCLC outcomes. PATIENTS AND METHODS: We performed a nationwide cohort study of patients newly diagnosed with NSCLC between 1997 and 2013 using the Taiwan Cancer Registry and Taiwan National Health Insurance databases. We identified patients who were treated with first-line EGFR TKIs and analyzed the association between use of PPIs and TKI treatment outcome. We defined the coverage ratio of PPIs as duration of PPI treatment in days divided by duration of TKIs in days. Patients who exhibited an overlap of >20% between PPI and TKI usage days were defined as having a high coverage ratio. RESULTS: A total of 1278 patients were treated with first-line gefitinib, 309 of which took PPIs at the same time and 145 had a high PPI coverage ratio. Patients had similar time to failure regardless of their PPI coverage ratio during gefitinib treatment. However, higher PPI coverage ratio significantly decreased overall survival (OS) compared with that of patients with a lower PPI coverage ratio or no PPI treatment in univariate analysis (median OS, 13.5, 16.7, and 21.8 months, respectively, p<0.01) and multivariate analyses (high coverage ratio HR: 1.67; low coverage ratio HR: 1.29). Exposure to PPIs during first line gefitinib treatment significantly decreased overall survival of patients with NSCLC. CONCLUSION: Concurrent use of PPIs was associated with lower overall survival in patients with EGFR-mutant NSCLC under first-line gefitinib treatment.

More Impaired Dynamic Ventilatory Muscle Oxygenation in Congestive Heart Failure than in Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) often have dyspnea. Despite differences in primary organ derangement and similarities in secondary skeletal muscle changes, both patient groups have prominent functional impairment. With similar daily exercise performance in patients with CHF and COPD, we hypothesized that patients with CHF would have worse ventilatory muscle oxygenation than patients with COPD. This study aimed to compare differences in tissue oxygenation and blood capacity between ventilatory muscles and leg muscles and between the two patient groups. Demographic data, lung function, and maximal cardiopulmonary exercise tests were performed in 134 subjects without acute illnesses. Muscle oxygenation and blood capacity were measured using frequency-domain near-infrared spectroscopy (fd-NIRS). We enrolled normal subjects and patients with COPD and CHF. The two patient groups were matched by oxygen-cost diagram scores, New York Heart Association functional classification scores, and modified Medical Research Council scores. COPD was defined as forced expired volume in one second and forced expired vital capacity ratio ≤0.7. CHF was defined as stable heart failure with an ejection fraction ≤49%. The healthy subjects were defined as those with no obvious history of chronic disease. Age, body mass index, cigarette consumption, lung function, and exercise capacity were different across the three groups. Muscle oxygenation and blood capacity were adjusted accordingly. Leg muscles had higher deoxygenation (HHb) and oxygenation (HbO2) and lower oxygen saturation (SmO2) than ventilatory muscles in all participants. The SmO2 of leg muscles was lower than that of ventilatory muscles because SmO2 was calculated as HbO2/(HHb+HbO2), and the HHb of leg muscles was relatively higher than the HbO2 of leg muscles. The healthy subjects had higher SmO2, the patients with COPD had higher HHb, and the patients with CHF had lower HbO2 in both muscle groups throughout the tests. The patients with CHF had lower SmO2 of ventilatory muscles than the patients with COPD at peak exercise (p < 0.01). We conclud that fd-NIRS can be used to discriminate tissue oxygenation of different musculatures and disease entities. More studies on interventions on ventilatory muscle oxygenation in patients with CHF and COPD are warranted.