Prognostic Value of Pace Variability, a Novel 6MWT-Derived Feature, in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The 6-minute walk test (6MWT) is often used to evaluate chronic obstructive pulmonary disease (COPD) patients' functional capacity, with 6-minute walk distance (6MWD) and related measures being linked to mortality and hospitalizations. This study investigates the prognostic value of pace variability, a significant indicator in sports medicine, during the 6MWT for COPD patients. Patients and Methods: We retrospectively screened consecutive COPD patients who had been prospectively enrolled in a pay-for-performance program from January 2019 to May 2020 to determine their eligibility. Patient characteristics, including demographics, exacerbation history, and 6MWT data, were analyzed to investigate their potential associations with prognosis. The primary outcome was a composite of adverse events, including overall mortality or hospitalizations due to exacerbations during a 1-year follow-up period. To analyze the 6MWT data, we divided it into three 2-minute epochs and calculated the average walk speed for each epoch. We defined pace variability as the difference between the maximum and minimum average speed in a single 2-minute epoch, divided by the average speed for the entire 6-minute walk test. Results: A total of 163 patients with COPD were included in the study, and 19 of them (12%) experienced the composite adverse outcome. Multivariable logistic regression analyses revealed that two predictors were independently associated with the composite outcome: % predicted 6MWD <72 (adjusted odds ratio [aOR] 7.080; 95% confidence interval [CI] 1.481-33.847) and pace variability ≥0.39 (aOR 9.444; 95% CI 2.689-33.170). Patients with either of these adverse prognostic features had significantly worse composite outcome-free survival, with both log-rank P values less than 0.005. Notably, COPD patients with both adverse features experienced an especially poor outcome after 1 year. Conclusion: Patients with COPD who exhibited greater pace variability during the 6MWT had a significantly higher risk of overall mortality and COPD-related hospitalizations, indicating a worse prognosis.

Effectiveness of Nationwide COPD Pay-for-Performance Program on COPD Exacerbations in Taiwan.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has also imposed a substantial economic and social burden on the health care system. In Taiwan, a nationwide COPD pay-for-performance (P4P) program was designed to improve the quality of COPD-related care by introducing financial incentives for health care providers and employing a multidisciplinary team to deliver guideline-based, integrated care for patients with COPD, reducing adverse outcomes, especially COPD exacerbation. However, the results of a survey of the effectiveness of the pay-for-performance program in COPD management were inconclusive. To address this knowledge gap, this study evaluated the effectiveness of the COPD P4P program in Taiwan. METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance claims database and nationwide COPD P4P enrollment program records from June 2016 to December 2018. Patients with COPD were classified into P4P and non-P4P groups. Patients in the P4P group were matched at a ratio of 1:1 based on age, gender, region, accreditation level, Charlson Comorbidity Index (CCI), and inhaled medication prescription type to create the non-P4P group. A difference-in-difference analysis was used to evaluate the influence of the P4P program on the likelihood of COPD exacerbation, namely COPD-related emergency department (ED) visit, intensive care unit (ICU) admission, or hospitalization. RESULTS: The final sample of 14,288 patients comprised 7144 in each of the P4P and non-P4P groups. The prevalence of COPD-related ED visits, ICU admissions, and hospitalizations was higher in the P4P group than in the non-P4P group 1 year before enrollment. After enrollment, the P4P group exhibited a greater decrease in the prevalence of COPD-related ED visits and hospitalizations than the non-P4P group (ED visit: -2.98%, p<0.05, 95% confidence interval [CI]: -0.277 to -0.086; hospitalization: -1.62%, p<0.05, 95% CI: -0.232 to -0.020), whereas no significant difference was observed between the groups in terms of the changes in the prevalence of COPD-related ICU admissions. CONCLUSION: The COPD P4P program exerted a positive net effect on reducing the likelihood of COPD exacerbation, namely COPD-related ED visits and hospitalizations. Future studies should examine the long-term cost-effectiveness of the COPD P4P program.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Impact of patient-centred and family-centred care meetings on intensive care and resource utilisation in patients with terminal illness: a single-centre retrospective observational study in Taiwan.

OBJECTIVE: Shared decision making is essential for patients and their families when facing serious and life-threatening diseases. This study aimed to evaluate the impact of patient-centred and family-centred care meetings (PFCCM) on intensive measures and resource utilisation during end-of-life (EOL) hospitalisation among terminally ill patients. DESIGN AND SETTING: A retrospective cross-sectional study using electronic medical records was conducted in a tertiary referral medical centre in Taiwan. PARTICIPANTS: We identified 6843 deceased patients with terminal illness who either received or did not receive PFCCM during EOL hospitalisation between January 2013 and December 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients who were transferred to the intensive care unit (ICU). Those who underwent invasive or non-invasive mechanical ventilation, tracheostomy, haemodialysis and surgical intervention during the final hospitalisation were determined by the use of intensive care measures; secondary measures were individual total and daily medical expenditures. A generalised estimating equation (GEE) model was used to compare the differences between the two groups. OR and beta coefficients (ß) with 95% CI were estimated. RESULTS: This study identified 459 patients (6.7%) who received PFCCM during EOL hospitalisation. Multivariate analyses showed that patients who received PFCCM were less likely to have ICU admissions (OR 0.44, 95% CI 0.34 to 0.57), undergo surgical interventions (OR 0.74, 95% CI 0.58 to 0.95) and invasive mechanical ventilation (OR 0.50, 95% CI 0.38 to 0.66) during the final hospitalisation, after adjusting for patient demographics, clinical conditions and year of admission. Additionally, a significant decrease in daily medical expenditures was observed in PFCCM patients (ß -0.18, 95% CI -0.25 to -0.12) than in non-PFCCM patients. CONCLUSIONS: Patient-physician discussion through PFCCM is associated with less intensive care utilisation and daily medical expenditure during EOL hospitalisation in terminally ill patients.

Comparison between COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scores for evaluation of clinical symptoms, comorbidities and medical resources utilization in COPD patients.

BACKGROUND: The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed a new severity assessment system for emphasizing clinical symptom evaluation by COPD Assessment Test (CAT) or modified Medical Research Council (mMRC) dyspnea scores. The aim of the study was to evaluate the effectiveness of two scoring systems in evaluating COPD patients. METHODS: A population based cross-sectional study employing computer-assisted telephone interviewing system (CATI) for surveying the epidemiology of COPD in Taiwan. Among 6600 subjects recruited (age > 40), 404 subjects (6.1%) were diagnosed as COPD. The comorbidities, COPD-related symptoms, health care resources utilization were compared between CAT and mMRC. RESULTS: There were significant differences in all co-morbidities, symptom severity in favor of CAT as compared to mMRC. When comparing health care resources utilization, CAT and mMRC have equal effectiveness in evaluating patients with regular medical treatment. There were significant differences in emergency room visit and hospitalization in favor of mMRC. However, CAT was more effective in evaluating patients with ICU admission (P = 0.005). CONCLUSION: Compared with CAT and mMRC, there are individual benefits in the evaluation of clinical symptoms, co-morbidities and medical resources utilization for ER, hospitalization and ICU admission in COPD patients.

Validity of ICD9-CM codes to diagnose chronic obstructive pulmonary disease from National Health Insurance claim data in Taiwan.

PURPOSE: Claim data from Taiwan's National Health Insurance (NHI) database have previously been utilized in the study of COPD. However, there are limited data on the positive predictive value of claim data for COPD diagnosis. Therefore, this study aimed to characterize and validate the COPD cohort identified from the NHI research database. METHODS: This cross-sectional study compared records from claim data with those from a medical center. From 2007 to 2014, a COPD cohort was constructed from claim data using ICD9-CM codes for COPD. The diagnostic positive predictive value of these data was assessed with reference to physician-verified COPD. In addition, a multivariate logistic regression model was built to identify independent factors associated with the positive predictive value of COPD diagnosis by claim data. RESULTS: During the 8-year study period, a total of 12,127 subjects met the criterion of having two or more outpatient codes in 1 year or one or more inpatient COPD codes in their claim data. Of this total, the diagnosis of COPD was verified by physicians in 7,701 (63.5%) subjects. Applying a more stringent criterion - three or more outpatient codes or two or more inpatient codes - improved the diagnostic positive predictive value to 72.2%. Age ≥65 years and a claim for spirometry were the two most important factors associated with the positive predictive value of claim-data-defined COPD. Adding spirometry testing to diagnostic ICD9-CM codes for COPD increased the positive predictive value to 84.6%. CONCLUSION: This study emphasizes the importance of validation of disease-specific diagnosis prior to applying an administrative database in clinical studies. It also indicates the limitation of ICD9-CM codes alone in recognizing COPD patients within the NHI research database.

Trajectories of caregiver burden and related factors in family caregivers of patients with lung cancer.

OBJECTIVE: This study aimed to (1) identify the changes of 5 domains of family caregiver (FC) burden, overall burden, and its subtrajectories when caring for newly diagnosed advanced lung cancer patients during the first 6 months following cancer diagnosis; and (2) identify the FC-related and patient-related factors most associated with the overall FC burden and each of its subtrajectories. METHODS: A total of 150 newly diagnosed advanced lung cancer patient-FC dyads were recruited from a Taiwanese medical center. The overall FC burden was evaluated 4 times: before treatment, and 1, 3, and 6 months after treatment. The potential subtrajectory of the caregiver burden was investigated by latent class growth analysis. The FC-related and patient-related factors having the greatest effect on the overall FC burden and its subtrajectories over time were identified by generalized estimating equations. RESULTS: The highest level of burden domain was "Impact on daily schedule" over time. Generally, most of the FC reported a moderate level of overall burden over the investigation period. Three subtrajectories of the overall FC burden over time (% caregivers) were identified: high burden (34.7%), moderate burden (56.0%), and low burden (9.3%), respectively. The self-efficacy of FC was the strongest factor related to the changes of the FC's burden and burden in each subtrajectory. CONCLUSION: The results support the existing and different types of subtrajectories of the FC's burden. Health care professionals should provide care based on those differences. Further research to test interventions which integrate those important factors related to FC's burden, particularly FC's self-efficacy, is strongly suggested.

The unmet supportive care needs-what advanced lung cancer patients' caregivers need and related factors.

PURPOSE: To identify the unmet supportive care needs and related factors in caregivers of patients with advanced lung cancer. METHODS: A cross-sectional study of 166 lung cancer patient-caregivers dyads was recruited at a medical center. The supportive care needs, fatigue, and sleep disturbance of caregivers were collected. Patients were assessed for symptom severity, anxiety, and depression. Logistic regression was used to reveal the related factors of unmet supportive care needs. RESULTS: Of the 166 dyads surveyed, the top unmet needs were information needs, health care professional/health care service needs, and daily living needs. Patients' anxiety was positively correlated to overall caregiving needs, health care professional/health care service needs, interpersonal communication needs, and psychological/emotional needs of caregivers. The information needs and health care professional/health care service needs were related to the caregivers' fatigue. The sleep disturbance of caregivers was associated with their overall caregiving needs, daily living needs, and psychological/emotional needs. CONCLUSIONS: Future interventions to meet the needs of caregivers should include specific needs assessment and continuing education in caregiving.

COPD in Taiwan: a National Epidemiology Survey.

OBJECTIVES: To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors. METHODS: We conducted a random cross-sectional national survey of adults older than 40 years in Taiwan. Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health. Subjects with diagnosed COPD were subdivided by smoking status. Subjects who fulfilled the case definition of COPD and smoked were designated as "possible COPD". Participants who did not fit the case definition of COPD were asked only about their personal circumstances and smoking habits. Data from these groups were analyzed and compared. RESULTS: Of the 6,600 participants who completed the survey, 404 (6.1%) fulfilled the epidemiological case definition of COPD: 137 with diagnosed COPD and 267 possible COPD. The most common comorbidities of COPD were hypertension or cardiovascular diseases (36.1%). Subjects with definite COPD had significantly higher COPD Assessment Test scores than the possible COPD group (14.6±8.32 vs 12.6±6.49, P=0.01) and significantly more comorbid illnesses (P=0.01). The main risk factors contributing to health care utilization in each COPD cohort were higher COPD Assessment Test scores (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.26), higher modified Medical Research Council Breathlessness Scale scores (OR 1.97, 95% CI 1.11-3.51), and having more than one comorbidity (OR 5.19, 95% CI 1.05-25.61). CONCLUSION: With estimated prevalence of 6.1% in the general population, COPD in Taiwan has been underdiagnosed. Symptoms and comorbidities were independent risk factors for health care utilization in subjects with definite or possible COPD. There is an urgent need to raise awareness of the importance of early evaluation and prompt treatment for subjects with chronic airway symptoms.

Performance Assessment of the BluePoint MycoID Plus Kit for Identification of Mycobacterium tuberculosis, Including Rifampin- and Isoniazid-resistant Isolates, and Nontuberculous Mycobacteria.

The performance of the BluePoint MycoID plus kit (Bio Concept Corporation, Taichung, Taiwan), which was designed to simultaneously detect Mycobacterium tuberculosis (MTB), rifampin- and isoniazid-resistant MTB, and nontuberculous mycobacteria (NTM) was first evaluated with 950 consecutive positive cultures in Mycobacterium Growth Indicator Tube (MGIT) system (BACTEC, MGIT 960 system, Becton-Dickinson, Sparks) from clinical respiratory specimens. The discrepant results between kit and culture-based identification were finally assessed by 16S rRNA gene sequencing and clinical diagnosis. The accuracy rate of this kit for identification of all Mycobacterium species was 96.3% (905/940). For MTB identification, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the kit were 99.7%, 99.3%, 99.0% and 99.8%, respectively. For rifampicin-resistant MTB identification, the sensitivity, specificity, PPV, and NPV of the kit were 100.0%, 99.4%, 91.3%, and 100.0%, respectively, while the corresponding values of isoniazid-resistant MTB identification were 82.6%, 99.4%, 95.0%, and 97.6%, respectively. In identifying specific NTM species, the kit correctly identified 99.3% of M. abscessus (147/148) complex, 100% of M. fortuitum (32/32), M. gordonae (38/38), M. avium (39/39), M. intracellulare (90/90), M. kansasii (36/36), and M. avium complex species other than M. avium and M. intracellulare (94/94). In conclusions, the diagnostic value of the BluePoint MycoID plus kit was superior to culture method for recoveries and identification of NTM to species level. In addition, the diagnostic accuracy of BluePoint MycoID plus kit in MTB identification was similar to conventional culture method with high accuracy rate of rifampicin-resistant M. tuberculosis identification.

Cost per QALY (quality-adjusted life year) and lifetime cost of prolonged mechanical ventilation in Taiwan.

INTRODUCTION: Patients who require prolonged mechanical ventilation (PMV) are increasing and producing financial burdens worldwide. This study determines the cost per QALY (quality-adjusted life year), out-of-pocket expenses, and lifetime costs for PMV patients stratified by underlying diseases and cognition levels. METHODS: A nationwide sample of 50,481 patients with continual mechanical ventilation for more than 21 days was collected during 1997-2007. After stratifying the patients according to specific diagnoses, a latent class analysis (LCA) was performed to categorise PMV patients with multiple co-morbidities into several homogeneous groups. The survival functions were estimated for individual groups using the Kaplan-Meier method and extrapolated to 300 months through a semi-parametric method. The survival functions were adjusted using an EQ-5D utility value derived from a convenience sample of 142 PMV patients to estimate quality-adjusted life expectancies (QALE). Another convenience sample of 165 patients was used to estimate the out-of-pocket expenses. The lifetime expenditures paid by the single-payer National Health Insurance (NHI) system and patients' families were estimated by multiplying average monthly expenditures by the survival probabilities and summing the values over lifetime. RESULTS: PMV therapy costs more than 100,000 U.S. dollars (USD) per QALY for all patients with poor cognition. For patients with partial cognition, PMV therapy costs less than 56,000 USD per QALY for those with liver cirrhosis, intracranial or spinal cord injuries, and 57,000-69,000 USD for patients with multiple co-morbidities under age of 65. The average lifetime cost of PMV was usually below 56,000 USD. The out-of-pocket expenses were often more than one-third of the total cost of treatment. CONCLUSIONS: PMV treatment for patients with poor cognition would cost more than 5 times Taiwan's GDP (gross domestic products), or less cost-effective. The out-of-pocket expenses for PMV provision should also be considered in policy decision.

Performance assessment of the DR. TBDR/NTM IVD kit for direct detection of Mycobacterium tuberculosis isolates, including rifampin-resistant isolates, and nontuberculous Mycobacteria.

We evaluated the performance of the DR. TBDR/NTM IVD kit, which was designed to detect Mycobacterium tuberculosis, rifampin-resistant M. tuberculosis, and nontuberculous mycobacteria, for detecting 110 positive and 50 negative cultures in Mycobacterium Growth Indicator Tubes. The accuracy rate of this kit for identification of Mycobacterium species was 95.5% (105/110).

Estimation of quality-adjusted life expectancy in patients under prolonged mechanical ventilation.

OBJECTIVES: The purpose of this study was to estimate the quality-adjusted life expectancy (QALE) and the expected lifetime utility loss of patients with prolonged mechanical ventilation (PMV). METHODS: PMV was defined as more than 21 days of mechanical ventilation. A total of 633 patients fulfilled this definition and were followed for 9 years (1998-2007) to obtain their survival status. Quality of life of 142 patients was measured with the EuroQol five-dimensional (EQ-5D) questionnaire during the period 2008 to 2009. The survival probabilities for each time point were adjusted with a utility measurement of quality of life and then extrapolated to 300 months to obtain the QALE. We compared the age-, gender-matched reference populations to calculate the expected lifetime utility loss. RESULTS: The average age of subjects was 76 years old. The life expectancy and loss of life expectancy were 1.95 years and 8.48 years, respectively. The QALE of 55 patients with partial cognitive ability and the ability to respond was 0.58 quality-adjusted life years (QALY), whereas the QALEs of 87 patients with poor consciousness were 0.28 and 0.29 QALY for the EQ-5D measured by family caregivers and nurses, respectively. The loss of QALE for PMV patients was 9.87 to 10.17 QALY, corresponding to a health gap of 94% to 97%. CONCLUSIONS: Theses results of poor prognosis would provide stakeholders evidence for communication to facilitate clinical decisions. The estimation may be used in future studies to facilitate the cost-effectiveness and reduction of the health gap.

Incidence and significance of clinically abnormal events in a tertiary referral medical center: implementation of the clinical alert system (CAS).

BACKGROUND: The prognosis of in-hospital cardiopulmonary arrest remains very poor. Reports have shown patients often have clinically abnormal events prior to arrest. To improve patient outcome and prevent arrest, detection of the abnormal events with early intervention has been advocated. However, the incidence of these events in Taiwan and their clinical significance remain unclear. METHODS: We conducted a prospective observational study with the implementation of the clinical alert system (CAS) in a university-affiliated tertiary referral medical center. Clinically abnormal events were detected using the CAS criteria for acute physiologic deterioration, and reported to experienced physicians for management. Patient and report data were retrieved, collected and analyzed. RESULTS: During the 14-month study period, a total of 2,050 events were detected in 1,640 patients. The estimated incidence of the events was 3.19 per 1,000 bed-days, which occurred in 2.14% of admissions. The most common event was abnormal heart rate (36.5%), followed by desaturation (26.7%), abnormal respiratory rate (24.5%), and abnormal blood pressure (23.1%). The majority of the events were reported in the day time, and nurses contributed most of the reports (66.4%). The 30-day and in-hospital mortality rates were 26.3% and 34%, respectively. Multivariate survival analysis showed that desaturation (relative risk [RR] = 1.715; p < 0.001), abnormal respiratory rate (RR = 1.652; p < 0.001), abnormal blood pressure (RR = 1.460; p = 0.001), coma (RR = 1.918; p < 0.001), and oliguria (RR = 1.424; p = 0.0024) were significantly associated with 30-day mortality. Mortality of patients in the last 2 months was significantly lower than that in the first 2 months (20.5% vs. 35.4%; p < 0.001), which suggests the effectiveness of the CAS. CONCLUSION: The development of clinically abnormal events is associated with poor outcome, which suggests that early detection and timely management of these events is necessary. Implementation of the CAS may improve the in-hospital outcome of these patients.

Performance assessment of the Capilia TB assay and the BD ProbeTec ET system for rapid culture confirmation of Mycobacterium tuberculosis.

Because of the increasing numbers of nontuberculous mycobacterial isolates from clinical specimens, rapid and accurate methods for culture confirmation of Mycobacterium tuberculosis are urgently needed. The study evaluated the performance of the Capilia TB immunochromatographic assay (TAUNS, Numazu, Japan) for culture confirmation of M. tuberculosis using 242 culture-positive liquid media in 2 mycobacterial laboratories from November 2005 to February 2006. Among the 242 samples, 183 were also tested with the BD ProbeTec ET (CTB) assay (Becton Dickinson, Sparks, MD). The results of both assays were compared to the culture results and to each other. The overall sensitivity and specificity of the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 97.3% and 97.1%, respectively. The positive and negative predictive values for the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 98.2% and 95.8%, respectively. Among the 183 samples tested with both assays, 8 had discrepant results, including Capilia-TB-false-positive in 2, CTB-false-positive in another 2, CTB-false-negative in 2, Capilia TB-false-negative in 1, and both assays with false-negative results in the remaining one. This study demonstrated that the Capilia TB assay has a similar diagnostic value with the CTB assay. In addition, with the immunochromatographic method, it is less time-consuming and does not require other laboratory equipment.