Chaicharn Pothirat

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

Objectives:To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design:Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. Setting:Two hundred and thirty-three ICUs in 17 countries. Patients:All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. Interventions: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. Measurements and Main Results: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. Conclusions: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.

Varenicline for smoking cessation: A placebo-controlled, randomized study

Background and objective:  Varenicline tartrate, a novel, selective, nicotinic acetylcholine receptor partial agonist, has been developed specifically as a smoking cessation drug. This study evaluated the efficacy of a standard regimen of varenicline compared with placebo for smoking cessation in 333 subjects in China, Singapore and Thailand.

An Outbreak of Botulism in Thailand: Clinical Manifestations and Management of Severe Respiratory Failure

BACKGROUND Northern Thailands biggest botulism outbreak to date occurred on 14 March 2006 and affected 209 people. Of these, 42 developed respiratory failure, and 25 of those who developed respiratory failure were referred to 9 high facility hospitals for treatment of severe respiratory failure and autonomic nervous system involvement. Among these patients, we aimed to assess the relationship between the rate of ventilator dependence and the occurrence of treatment by day 4 versus day 6 after exposure to bamboo shoots (the source of the botulism outbreak), as well as the relationship between ventilator dependence and negative inspiratory pressure. METHODS We reviewed the circumstances and timing of symptoms following exposure. Mobile teams treated patients with botulinum antitoxin on day 4 or day 6 after exposure in Nan Hospital (Nan, Thailand). Eighteen patients (in 7 high facility hospitals) with severe respiratory failure received a low- and high-rate repetitive nerve stimulation test, and negative inspiratory pressure was measured. RESULTS Within 1-65 h after exposure, 18 of the patients with severe respiratory failure had become ill. The typical clinical sequence was abdominal pain, nausea and/or vomiting, diarrhea, dysphagia and/or dysarthria, ptosis, diplopia, generalized weakness, urinary retention, and respiratory failure. Most patients exhibited fluctuating pulse and blood pressure. Repetitive nerve stimulation test showed no response in the most severe stage. In the moderately severe stage, there was a low-amplitude compound muscle action potential with a low-rate incremented/high-rate decremented response. In the early recovery phase, there was a low-amplitude compound muscle action potential with low- and high-rate incremented response. In the ventilator-weaning stage, there was a normal-amplitude compound muscle action potential. Negative inspiratory pressure variation among 14 patients undergoing weaning from mechanical ventilation was observed. Kaplan-Meier survival analysis identified a shorter period of ventilator dependency among patients receiving botulinum antitoxin on day 4 (P=.02). CONCLUSIONS Patients receiving botulinum antitoxin on day 4 had decreased ventilator dependency. In addition, for patients with foodborne botulism, an effective referral system and team of specialists are needed.

Survey of asthma control in Thailand.

Objective:  The aim of the study was to determine whether asthma management in Thailand is succeeding in achieving the levels of control, specified in national and international asthma guidelines.

Ventilator-Associated Pneumonia: Epidemiology and Prognostic Indicators of 30-Day Mortality

We conducted a retrospective cohort study in the medical intensive care unit of Chaing Mai University Hospital to describe the epidemiology of ventilator-associated pneumonia (VAP) and identify prognostic indicators of 30-day VAP mortality. A total of 621 patients diagnosed with VAP between January 2005 and December 2011 were included. The overall 30-day mortality rate was 44.4%. The major causative pathogens were Acinetobacter baumannii (54.3%), Pseudomonas aeruginosa (35.2%), and methicillin-resistant Staphylococcus aureus (15.1%). Most A. baumannii (90.2%) comprised drug-resistant strains. Identified prognostic indicators were co-morbid malignancy (hazard ratio [HR] = 1.60; 95% confidence interval [CI] 1.02-2.42; P = 0.040), septic shock (HR = 2.51; 95% CI, 1.60-4.00; P < 0.001), Simplified Acute Physiology Score II >45 (HR = 1.62; 95% CI, 1.03-2.56; P = 0.041), Sequential Organ Failure Assessment score >5 (HR = 3.40; 95% CI 2.00-5.81; P < 0.001), and delayed inappropriate empirical antibiotic treatment (HR = 2.23; 95% CI, 1.12-4.45; P = 0.022). VAP was associated with high mortality. The major causative pathogen was drug-resistant A. baumannii. Therefore, early detection of VAP by surveillance in mechanically ventilated patients leading to earlier treatment may improve patient outcomes. Guidelines for prescribing appropriate empirical antibiotics to cover drug-resistant bacteria could be established using local epidemiological data.

evaluating inhaler use technique in COPD patients

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.

Long-term efficacy of intensive cycle ergometer exercise training program for advanced COPD patients.

Background Exercise training has been incorporated into the international guidelines for the treatment of chronic obstructive pulmonary disease (COPD). However, the long-term efficacy of the training program for patients with advanced COPD has never been evaluated in Thailand. Purpose To determine the long-term efficacy of intensive cycle ergometer exercise program on various clinical parameters of patients with advanced COPD. Materials and methods The patients with advanced COPD were separated into two groups: the intensive ergometer exercise program group and the control group. The clinical parameters of all the patients were assessed at baseline, every month for the first 3 months, and then every 3 months until they had completed the 24-month follow-up. Mann–Whitney U test was used to compare baseline mean differences between the groups. Repeated measure analysis was applied to determine the progress in all parameters during the entire follow-up period. Mean incase imputation method was applied to estimate the parameters of dropout cases. Results A total of 41 patients were enrolled: 27 in the intensive ergometer exercise program group and 14 in the control group. The intensive cycle ergometer exercise program group showed statistically significant improvements in muscle strength (from month 1 till the end of the study, month 24), endurance time (from month 1 till the end of measurement, month 12) and clinically significant improvements in 6-minute walk distance (from month 2 until month 9), dyspnea severity by transitional dyspnea index (from month 1 till the end of the study, month 24), and quality of life (from month 1 till the end of the study, month 24). There was no significant difference in survival rates between the groups. Conclusion The intensive ergometer exercise training program revealed meaningful long-term improvements in various clinical parameters for up to 2 years. These promising results should encourage health care professionals to promote exercise training for patients with advanced COPD who have limited daily activities despite optimal medication control.

Detection of acute deterioration in health status visit among COPD patients by monitoring COPD assessment test score

Background The Chronic Obstructive Pulmonary Disease Assessment Test (CAT) could play a role in detecting acute deterioration in health status during monitoring visits in routine clinical practice. Objective To evaluate the discriminative property of a change in CAT score from a stable baseline visit for detecting acute deterioration in health status visits of chronic obstructive pulmonary disease (COPD) patients. Methods The CAT questionnaire was administered to stable COPD patients routinely attending the chest clinic of Chiang Mai University Hospital who were monitored using the CAT score every 1–3 months for 15 months. Acute deterioration in health status was defined as worsening or exacerbation. CAT scores at baseline, and subsequent visits with acute deterioration in health status were analyzed using the t-test. The receiver operating characteristic curve was performed to evaluate the discriminative property of change in CAT score for detecting acute deterioration during a health status visit. Results A total of 354 follow-up visits were made by 140 patients, aged 71.1±8.4 years, with a forced expiratory volume in 1 second of 47.49%±18.2% predicted, who were monitored for 15 months. The mean CAT score change between stable baseline visits, by patients’ and physicians’ global assessments, were 0.05 (95% confidence interval [CI], −0.37–0.46) and 0.18 (95% CI, −0.23–0.60), respectively. At worsening visits, as assessed by patients, there was significant increase in CAT score (6.07; 95% CI, 4.95–7.19). There were also significant increases in CAT scores at visits with mild and moderate exacerbation (5.51 [95% CI, 4.39–6.63] and 8.84 [95% CI, 6.29–11.39], respectively), as assessed by physicians. The area under the receiver operating characteristic curve of CAT score change for the detection of acute deterioration in health status was 0.89 (95% CI, 0.84–0.94), and the optimum cut-off point score was at 4, with a sensitivity, specificity, and accuracy of 76.8%, 83.6%, and 82.4%, respectively. Conclusions Change in CAT score during monitoring visits is useful for detecting acute deterioration in health status, and a change of 4 units could make a moderate prediction of acute deterioration in health status.

Prognostic factors associated with mortality of drug-resistant Acinetobacter baumannii ventilator-associated pneumonia.

BackgroundVentilator-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.MethodsA 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.ResultsA 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).ConclusionsDrug-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.

Peak expiratory flow rate as a surrogate for forced expiratory volume in 1 second in COPD severity classification in Thailand.

Background There are limited studies directly comparing correlation and agreement between peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1) for severity classification of COPD. However, clarifying the role of PEFR as a surrogate of COPD severity classification instead of FEV1 is essential in situations and areas where spirometry is not routinely available. Purpose To evaluate the agreement between FEV1 and PEFR using Global initiative for chronic Obstructive Lung Disease (GOLD) severity classification criteria. Materials and methods This cross-sectional study included stable COPD patients. Both absolute values and % predicted FEV1 and % predicted PEFR were obtained from the same patients at a single visit. The severity of COPD was classified according to GOLD criteria. Pearson’s correlation coefficient was used to examine the relationship between FEV1 and PEFR. The agreement of % predicted FEV1 and % predicted PEFR in assigning severity categories was calculated using Kappa statistic, and identification of the limits of agreement was by Bland–Altman analysis. Statistical significance was set at P-value <0.05. Results Three hundred stable COPD patients were enrolled; 195 (65.0%) male, mean age 70.4±9.4 years, and mean % predicted FEV1 51.4±20.1. Both correlations between the % predicted FEV1 and PEFR as well as the absolute values were strongly significant (r=0.76, P<0.001 and r=0.87, P<0.001, respectively). However, severity categories of airflow limitation based on % predicted FEV1 or PEFR intervals were concordant in only 179 patients (59.7%). The Kappa statistic for agreement was 0.41 (95% confidence interval, 0.34–0.48), suggesting unsatisfied agreement. The calculated limits of agreement were wide (+27.1% to −28.9%). Conclusion Although the correlation between FEV1 and PEFR measurements were strongly significant, the agreement between the two tests was unsatisfied and may influence inappropriate clinical decision making in diagnosis, severity classification, and management of COPD.