To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. Two hundred and thirty-three ICUs in 17 countries. All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran–Mantel–Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

Ceftaroline, the active form of the prodrug ceftaroline fosamil, is a novel cephalosporin with bactericidal activity against important pathogens associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and common Gram-negative pathogens. FOCUS 1 is a randomized, double-blinded, Phase III study that was conducted to evaluate the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) ≥ −10%] in clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations. Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Patients also received two 500 mg doses of oral clarithromycin every 12 h administered on day 1. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 1 registration number NCT00621504 (http://clinicaltrials.gov/ct2/show/NCT00621504). Of 613 enrolled patients, 298 received ceftaroline fosamil and 308 received ceftriaxone. Baseline characteristics between treatment groups were comparable. Clinical cure rates were as follows: CE population, 86.6% (194/224) for ceftaroline fosamil and 78.2% (183/234) for ceftriaxone [difference (95% CI), 8.4% (1.4, 15.4)]; and MITTE population, 83.8% (244/291) for ceftaroline fosamil and 77.7% (233/300) for ceftriaxone [difference (95% CI), 6.2% (−0.2, 12.6)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE population were 88.9% (24/27) and 66.7% (20/30) for ceftaroline fosamil and ceftriaxone, respectively. Both agents were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations because of an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, insomnia and nausea, and the most common AEs for ceftriaxone-treated patients were hypokalaemia, hypertension, nausea and diarrhoea. Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.

Chiang Dao is one of the districts in Chiang Mai, Thailand facing high level of seasonal air pollution every year, the exposure of community dwellers to outdoor air pollutants 24 hours a day during seasonal smog period because of their open-air housing style, and agricultural occupational hazard. In addition, Chiang Dao hospital is the only available hospital serving the community with open-air wards; therefore we could certainly to identify the association between air pollution and mortality of hospitalized patients. Thus, the aim of this study was to determine the association between daily average seasonal air pollutants and daily mortality of hospitalized patients and community dwellers as well as emergency and hospitalization visits for serious respiratory, cardiovascular, and cerebrovascular diseases. This time series study was conducted between 1 March 2016 and 31 March 2017. The association of various air pollutant concentrations including particulate matter diameter less than 10 and 2.5 microns (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3) and daily mortality of hospitalized patients and community dwellers as well as relationship with frequencies of serious respiratory, cardiovascular, and cerebrovascular diseases were analyzed using a general linear model with Poisson distribution. Only PM2.5 was found to be associated with increased daily mortality of hospitalized patients (lag day 6, adjusted RR =1.153, 95% CI: 1.001-1.329), whereas PM10, PM2.5, NO2, and O3 were associated with increased daily non-accidental mortality of community dwellers (lag day 0-7, adjusted RR =1.006-1.040, 95% CI: 1.000-1.074). For acute serious respiratory events; PM10 and PM2.5 were associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), while SO2, CO, and O3 were associated with emergency visits for community-acquired pneumonia (CAP). O3 was associated with emergency visits for heart failure (HF), NO2 with emergency visits for myocardial infarction (MI), and SO2 with hospitalized visits for cerebrovascular accident (CVA). Seasonal air pollutants were found to be associated with higher mortality among hospitalized patients and community dwellers with varying effects on severe acute respiratory, cardiovascular, and cerebrovascular diseases.

Ventilator-associated pneumonia (VAP) caused by drug-resistant Acinetobacter baumannii is associated with high mortality in critically ill patients. We identified the prognostic factors of 30-day mortality in patients with VAP caused by drug-resistant A. baumannii and compared survival outcomes among multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) A. baumannii VAP. A retrospective cohort study was conducted in the Medical Intensive Care Unit at Chiang Mai University Hospital, Thailand. All adult patients diagnosed with A. baumannii VAP between 2005 and 2011 were eligible. Univariable and multivariable Cox’s proportional hazards regression were performed to identify the prognostic factors of 30-day mortality. A total of 337 patients with microbiologically confirmed A. baumannii VAP were included. The proportion of drug-sensitive (DS), MDR, XDR, and PDR A. baumannii were 9.8%, 21.4%, 65.3%, and 3.6%, respectively. The 30-day mortality rates were 21.2%, 31.9%, 56.8%, and 66.7%, respectively. The independent prognostic factors were SOFA score >5 (hazard ratio (HR) = 3.33, 95% confidence interval (CI) 1.94–5.72, P < 0.001), presence of septic shock (HR = 2.66, 95% CI 1.71–4.12, P < 0.001), Simplified Acute Physiology Score (SAPS) II >45 (HR = 1.58, 95% CI 1.01–2.46, P = 0.045), and inappropriate initial antibiotic treatment (HR = 1.53, 95% CI 1.08–2.20, P = 0.016). Drug-resistant A. baumannii, particularly XDR and PDR, was associated with a high mortality rate. Septic shock, high SAPS II, high SOFA score, and inappropriate initial antibiotic treatment were independent prognostic factors for 30-day mortality.

Background: Poor inhalation techniques are associated with decreased medication delivery and poor disease control in chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate techniques for using inhaler devices in COPD patients. Methods: A prospective cross-sectional study was conducted to assess patient compliance with correct techniques for using inhaler devices across four regimens, ie, the pressurized metered-dose inhaler (pMDI), the pMDI with a spacer, the Accuhaler^®, and the Handihaler^®. The percentage of compliance with essential steps of correct device usage for each regimen was recorded without prior notification when COPD patients presented for a routine visit, and 1 month after receiving face-to-face training. We compared the percentage of compliance between the devices and risk factors related to incorrect techniques using logistic regression analysis. Percentage of patient compliance with correct techniques was compared between the two visits using the chi-square test. Statistical significance was set at P<0.05. Results: A total of 103 COPD patients (mean age 71.2±9.2 years, males 64.1%, low education level 82.5%, and percent predicted forced expiratory volume in 1 second 51.9±22.5) were evaluated. Seventy-seven patients (74.8%) performed at least one step incorrectly. Patients using the Handihaler had the lowest compliance failure (42.5%), and the odds ratio for failure with the other devices compared with the Handihaler were 4.6 (95% confidence interval [CI] 1.8–11.8) for the pMDI, 3.1 (95% CI 1.2–8.2) for the pMDI with a spacer, and 2.4 (95% CI 1.1–5.2) for the Accuhaler. Low education level was the single most important factor related to incorrect technique (adjusted odds ratio 4.1, 95% CI 1.2–13.4, P=0.022). Formal training resulted in a statistically significant decrease in percentage of incorrect techniques for all devices and for the pMDI (59.4% vs 48.6%, P<0.001; 72.4% vs 48.3%, P=0.039, respectively). Conclusion: Inhalation technique in COPD patients without face-to-face training was mostly unsatisfactory, especially in patients with low education levels. The Handihaler was the inhaler device associated with the lowest technique failure. Face-to-face inhalation technique training significantly increased technique compliance for the pMDI.