The contribution of estimated dead space fraction to mortality prediction in patients with chronic obstructive pulmonary disease-a new proposal.

Background: Mortality due to chronic obstructive pulmonary disease (COPD) is increasing. However, dead space fractions at rest (VD/VTrest) and peak exercise (VD/VTpeak) and variables affecting survival have not been evaluated. This study aimed to investigate these issues. Methods: This retrospective observational cohort study was conducted from 2010-2020. Patients with COPD who smoked, met the Global Initiatives for Chronic Lung Diseases (GOLD) criteria, had available demographic, complete lung function test (CLFT), medication, acute exacerbation of COPD (AECOPD), Charlson Comorbidity Index, and survival data were enrolled. VD/VTrest and VD/VTpeak were estimated (estVD/VTrest and estVD/VTpeak). Univariate and multivariable Cox regression with stepwise variable selection were performed to estimate hazard ratios of all-cause mortality. Results: Overall, 14,910 patients with COPD were obtained from the hospital database, and 456 were analyzed after excluding those without CLFT or meeting the lung function criteria during the follow-up period (median (IQR) 597 (331-934.5) days). Of the 456 subjects, 81% had GOLD stages 2 and 3, highly elevated dead space fractions, mild air-trapping and diffusion impairment. The hospitalized AECOPD rate was 0.60 ± 2.84/person/year. Forty-eight subjects (10.5%) died, including 30 with advanced cancer. The incidence density of death was 6.03 per 100 person-years. The crude risk factors for mortality were elevated estVD/VTrest, estVD/VTpeak, ≥2 hospitalizations for AECOPD, advanced age, body mass index (BMI) <18.5 kg/m2, and cancer (hazard ratios (95% C.I.) from 1.03 [1.00-1.06] to 5.45 [3.04-9.79]). The protective factors were high peak expiratory flow%, adjusted diffusing capacity%, alveolar volume%, and BMI 24-26.9 kg/m2. In stepwise Cox regression analysis, after adjusting for all selected factors except cancer, estVD/VTrest and BMI <18.5 kg/m2 were risk factors, whereas BMI 24-26.9 kg/m2 was protective. Cancer was the main cause of all-cause mortality in this study; however, estVD/VTrest and BMI were independent prognostic factors for COPD after excluding cancer. Conclusions: The predictive formula for dead space fraction enables the estimation of VD/VTrest, and the mortality probability formula facilitates the estimation of COPD mortality. However, the clinical implications should be approached with caution until these formulas have been validated.

Sensitivity analysis of selection bias: a graphical display by bias-correction index.

Background: In observational studies, how the magnitude of potential selection bias in a sensitivity analysis can be quantified is rarely discussed. The purpose of this study was to develop a sensitivity analysis strategy by using the bias-correction index (BCI) approach for quantifying the influence and direction of selection bias. Methods: We used a BCI, a function of selection probabilities conditional on outcome and covariates, with different selection bias scenarios in a logistic regression setting. A bias-correction sensitivity plot was illustrated to analyze the associations between proctoscopy examination and sociodemographic variables obtained using the data from the Taiwan National Health Interview Survey (NHIS) and of a subset of individuals who consented to having their health insurance data further linked. Results: We included 15,247 people aged ≥20 years, and 87.74% of whom signed the informed consent. When the entire sample was considered, smokers were less likely to undergo proctoscopic examination (odds ratio (OR): 0.69, 95% CI [0.57-0.84]), than nonsmokers were. When the data of only the people who provided consent were considered, the OR was 0.76 (95% CI [0.62-0.94]). The bias-correction sensitivity plot indicated varying ORs under different degrees of selection bias. Conclusions: When data are only available in a subsample of a population, a bias-correction sensitivity plot can be used to easily visualize varying ORs under different selection bias scenarios. The similar strategy can be applied to models other than logistic regression if an appropriate BCI is derived.

Risk reduction analysis of mix-and-match vaccination strategy in healthcare workers during SARS-CoV-2 Omicron variant predominant period: A multi-center cohort study in Taiwan.

This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P < .001) of acquiring infection, respectively. Our study demonstrated that mix-and-match vaccination strategy may be associated with different level of risk reduction in acquiring infection, and sizable, prospective studies are encouraged to further elucidate our observation.

Influenza vaccination is associated with a reduced risk of invasive aspergillosis in high-risk individuals in Taiwan: a population-based cohort study.

Invasive aspergillosis (IA) has become the emerging life-threatening disease in recent years. Influenza has been identified as an independent risk factor for IA. Vaccination is the most effective way to prevent influenza, while whether it can reduce IA in high-risk population still uncertain. We aimed to investigate the association between influenza vaccination and the risk of IA in high-risk population. We performed a population-based cohort study of people who qualified for government-funded influenza vaccination and were at high risk for IA at the start of the influenza season each year between 2016 and 2019. We utilized Taiwan's National Health Insurance Research Database to identify the influenza vaccination status and IA diagnosis during the follow-up period. We compared the risk of IA between people with and without vaccination using multivariable logistic regression analysis. Out of total 8,544,451 people who were eligible during the 3 influenza seasons, 3,136,477 (36.7%) were vaccinated. A total of 1179 IA cases with the incidence of 13.8 cases per 100,000 high-risk individuals were identified during the follow-up. Compared to non-vaccinated group, vaccinated individuals had a 21% risk reduction of IA (adjusted odds ratio 0.79, 95% confidence interval 0.70-0.90). Influenza vaccination was associated with a lower risk of IA among males, immunosuppressive conditions, malignancy, diabetes, and those having host factors according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Influenza vaccination is recommended for high-risk population to reduce the risk of IA.

The Impact of the COVID-19 Pandemic on Tuberculosis Case Notification and Treatment Outcomes in Eswatini.

Objectives: We investigated the impact of COVID-19 on tuberculosis (TB) case notification and treatment outcomes in Eswatini. Methods: A comparative retrospective cohort study was conducted using TB data from eight facilities. An interrupted time series analysis, using segmented Poisson regression was done to assess the impact of COVID-19 on TB case notification comparing period before (December 2018-February 2020, n = 1,560) and during the pandemic (March 2020-May 2021, n = 840). Case notification was defined as number of TB cases registered in the TB treatment register. Treatment outcomes was result assigned to patients at the end of treatment according to WHO rules. Results: There was a significant decrease in TB case notification (IRR 0.71, 95% CI: 0.60-0.83) and a significant increase in death rate among registrants during the pandemic (21.3%) compared to pre-pandemic (10.8%, p < 0.01). Logistic regression indicated higher odds of unfavorable outcomes (death, lost-to-follow-up, and not evaluated) during the pandemic than pre-pandemic (aOR 2.91, 95% CI: 2.17-3.89). Conclusion: COVID-19 negatively impacted TB services in Eswatini. Eswatini should invest in strategies to safe-guard the health system against similar pandemics.

An Immunobridging Study to Evaluate the Neutralizing Antibody Titer in Adults Immunized with Two Doses of Either ChAdOx1-nCov-19 (AstraZeneca) or MVC-COV1901.

Rapid development and deployment of vaccines is crucial to control the continuously evolving COVID-19 pandemic. The placebo-controlled phase 3 efficacy trial is still the standard for authorizing vaccines in the majority of the world. However, due to a lack of eligible participants in parts of the world, this has not always been feasible. Recently, the Taiwan Food and Drug Administration, following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data. Here, we describe a study in which our candidate vaccine, MVC-COV1901, an adjuvanted protein subunit vaccine, has been granted emergency use authorization (EUA) in Taiwan based on a noninferiority immunobridging study. Immunogenicity results from the per protocol immunogenicity (PPI) subset (n = 903) from the MVC-COV1901 phase 2 trial were compared with results from 200 subjects who had received an adenovirus vector vaccine, AstraZeneca ChAdOx nCOV-19 (AZD1222), in a separate study. The lower bound of the 95% confidence interval (CI) of the geometric mean titer (GMT) ratio comparing MVC-COV1901 to AZD1222 was 3.4. The lower bound of the 95% CI of the sero-response rate was 95.5%. Both the GMT ratio and sero-response rate exceeded the criteria established by the Taiwan regulatory authority, leading to EUA approval of MVC-COV1901 in Taiwan.

Prediction and types of dead-space fraction during exercise in male chronic obstructive pulmonary disease patients.

ABSTRACT: A high dead space (VD) to tidal volume (VT) ratio during peak exercise (VD/VTpeak) is a sensitive and consistent marker of gas exchange abnormalities; therefore, it is important in patients with chronic obstructive pulmonary disease (COPD). However, it is necessary to use invasive methods to obtain VD/VTpeak, as noninvasive methods, such as end-tidal PCO2 (PETCO2peak) and PETCO2 adjusted with Jones' equation (PJCO2peak) at peak exercise, have been reported to be inconsistent with arterial PCO2 at peak exercise (PaCO2peak). Hence, this study aimed to generate prediction equations for VD/VTpeak using statistical techniques, and to use PETCO2peak and PJCO2peak to calculate the corresponding VD/VTpeaks (i.e., VD/VTpeakETVD/VTpeakJ).A total of 46 male subjects diagnosed with COPD who underwent incremental cardiopulmonary exercise tests with PaCO2 measured via arterial catheterization were enrolled. Demographic data, blood laboratory tests, functional daily activities, chest radiography, two-dimensional echocardiography, and lung function tests were assessed.In multivariate analysis, diffusing capacity, vital capacity, mean inspiratory tidal flow, heart rate, and oxygen pulse at peak exercise were selected with a predictive power of 0.74. There were no significant differences in the PCO2peak values and the corresponding VD/VTpeak values across the three types (both p = NS).In subjects with COPD, VD/VTpeak can be estimated using statistical methods and the PETCO2peak and PJCO2peak. These methods may have similar predictive power and thus can be used in clinical practice.

Incidence and Risk Factors of Reinfection with HCV after Treatment in People Living with HIV.

Infection with hepatitis C virus (HCV) does not induce protective immunity, and re-exposure to HCV can reinfect the population engaging in high-risk behavior. An increasing incidence of acute hepatitis C infection in people living with HIV (PLWH) has been described in recent years. This retrospective cohort study was conducted in PLWH who completed HCV therapy between June 2009 and June 2020 at an HIV care hospital, to analyze their basic characteristics and risky behavior. Of 2419 patients, 639 were diagnosed with HCV infection and 516 completed the HCV therapy with a sustained virologic response. In total, 59 patients (11.4%) were reinfected with acute hepatitis C, and the median time to reinfection was 85.3 weeks (IQR: 57-150). The incidence of reinfection was 6.7 cases/100 person-years. The factors associated with reinfection were being male (AHR, 8.02; 95% CI 1.08-59.49), DAA (direct-acting antiviral) treatment (AHR, 2.23; 95% CI 1.04-4.79), liver cirrhosis (AHR, 3.94; 95% CI 1.09-14.22), heroin dependency (AHR: 7.41; 95% CI 3.37-14.3), and HIV viral loads <50 copies/mL at the follow-up (AHR: 0.47, 95% CI 0.24-0.93) in the subgroup of people who inject drugs (PWID). Amphetamine abuse (AHR: 20.17; 95% CI 2.36-172.52) was the dominant factor in the subgroup of men who have sex with men (MSM). Our study suggests that education and behavioral interventions are needed in this population to prevent reinfection.

The Association Between Renal Function Decline and the Incidence of Urothelial Carcinoma: A 16-year Retrospective Cohort Study in Taiwan.

BACKGROUND: The incidence of cancer is higher among patients with end-stage renal disease but it remains uncertain whether a mild decrease in renal function affects cancer. OBJECTIVE: To measure the effect of impaired renal function, represented by the estimated glomerular filtration rate (eGFR), personal health behaviors, and long-term exposure to fine particulate matter (PM2.5) on the risk of urothelial carcinoma (UC) incidence. DESIGN SETTING AND PARTICIPANTS: We performed a population-based cohort study of 372 008 participants aged ≥30 yr with no prior cancer history using the MJ health examination database (2000-2015) and UC diagnosis data from the Taiwan Cancer Registry database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazards models were used to quantify the association between eGFR and UC incidence. RESULTS AND LIMITATIONS: We detected 383 UC cases during a median follow-up of 10.3 yr. Low eGFR was significantly associated with UC (p value for trend <0.01): compared to eGFR ≥90 ml/min/1.73 m2, the adjusted hazard ratio (HR) was 1.36 (95% confidence interval [CI] 0.98-1.88), 1.86 (95% CI 1.22-2.84), and 1.95 (95% CI 1.06-3.56) for eGFR strata of 60-89, 45-59, and <45 ml/min/1.73 m2, respectively. The risk remained elevated after stratifying the follow-up duration to check for reverse causality, and the dose-response relationship was stronger for women than for men. Current smoking (HR 1.34, 95% CI 1.02-1.77) and long-term exposure to PM2.5 concentrations ≥25.1 µg/m3 (HR 1.54, 95% CI 1.14-2.09) both significantly increased the risk of UC incidence. A significant dose-response relationship between PM2.5 and UC was also noted (p trend < 0.01). Limitations include the retrospective design and limited information on medical history. CONCLUSIONS: Lower renal function showed a dose-response relationship in elevating UC risk. Long-term exposure to PM2.5 is also a possible UC risk factor. PATIENT SUMMARY: People with kidney function that is lower than normal should monitor the health of their kidneys and other organs in the urinary system. Our study confirmed that as well as smoking, exposure to fine particulate matter in the air may be a risk factor for cancers of the urinary system.

Resting Dead Space Fraction as Related to Clinical Characteristics, Lung Function, and Gas Exchange in Male Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Measures of forced expired volume in one second % predicted (FEV1%), residual volume to total lung capacity ratio (RV/TLC) and diffusing capacity for carbon monoxide measurements (DLCO) are the standard lung function test for evaluating patients with chronic obstructive pulmonary disease (COPD). The dead space fraction (VD/VT) has been shown to be a robust marker of gas exchange abnormality. However, the use of VD/VT has gradually become less common. As VD/VT measured at rest (VD/VTR) has been successfully used in non-COPD conditions, it was hypothesized that in COPD the VD/VTR was more sensitive than the standard lung function test in correlation with clinical characteristics and gas exchange. This study aimed to test the hypothesis and to identify the variables relevant to VD/VTR. METHODS: A total of 46 male subjects with COPD were enrolled. Clinical characteristics included demographic data, oxygen-cost diagram (OCD), and image studies for pulmonary hypertension. The standard lung function was obtained. To calculate VD/VT, invasive arterial blood gas and pulmonary gas exchange (PGX) were measured. The variables relevant to VD/VTR were analyzed by multiple linear regression. RESULTS: Compared to lung function, VD/VTR was more frequently and significantly related to smoking, carboxyhemoglobin level, pulmonary hypertension and PaCO2 (all p <0.05) whereas FEV1% was more related to lung function test, PaO2 and OCD score. VD/VTR and FEV1% were highly related to resting gas exchange but RV/TLC and DLCO% were not. Cigarette consumption, the equivalent for CO2 output, arterial oxyhemoglobin saturation, and the product of tidal volume and inspiratory duty cycle were identified as the parameters relevant to VD/VTR with a power of 0.72. CONCLUSION: Compared to lung function test, VD/VTR is more related to clinical characteristics and is a comprehensive marker of resting gas exchange. Further studies are warranted to provide a noninvasive measurement of VD/VTR. REGISTRATION NUMBER: MOST 106-2314-B-040-025 and CSH-2019-C-30.

Applying Machine Learning Models with An Ensemble Approach for Accurate Real-Time Influenza Forecasting in Taiwan: Development and Validation Study.

BACKGROUND: Changeful seasonal influenza activity in subtropical areas such as Taiwan causes problems in epidemic preparedness. The Taiwan Centers for Disease Control has maintained real-time national influenza surveillance systems since 2004. Except for timely monitoring, epidemic forecasting using the national influenza surveillance data can provide pivotal information for public health response. OBJECTIVE: We aimed to develop predictive models using machine learning to provide real-time influenza-like illness forecasts. METHODS: Using surveillance data of influenza-like illness visits from emergency departments (from the Real-Time Outbreak and Disease Surveillance System), outpatient departments (from the National Health Insurance database), and the records of patients with severe influenza with complications (from the National Notifiable Disease Surveillance System), we developed 4 machine learning models (autoregressive integrated moving average, random forest, support vector regression, and extreme gradient boosting) to produce weekly influenza-like illness predictions for a given week and 3 subsequent weeks. We established a framework of the machine learning models and used an ensemble approach called stacking to integrate these predictions. We trained the models using historical data from 2008-2014. We evaluated their predictive ability during 2015-2017 for each of the 4-week time periods using Pearson correlation, mean absolute percentage error (MAPE), and hit rate of trend prediction. A dashboard website was built to visualize the forecasts, and the results of real-world implementation of this forecasting framework in 2018 were evaluated using the same metrics. RESULTS: All models could accurately predict the timing and magnitudes of the seasonal peaks in the then-current week (nowcast) (ρ=0.802-0.965; MAPE: 5.2%-9.2%; hit rate: 0.577-0.756), 1-week (ρ=0.803-0.918; MAPE: 8.3%-11.8%; hit rate: 0.643-0.747), 2-week (ρ=0.783-0.867; MAPE: 10.1%-15.3%; hit rate: 0.669-0.734), and 3-week forecasts (ρ=0.676-0.801; MAPE: 12.0%-18.9%; hit rate: 0.643-0.786), especially the ensemble model. In real-world implementation in 2018, the forecasting performance was still accurate in nowcasts (ρ=0.875-0.969; MAPE: 5.3%-8.0%; hit rate: 0.582-0.782) and remained satisfactory in 3-week forecasts (ρ=0.721-0.908; MAPE: 7.6%-13.5%; hit rate: 0.596-0.904). CONCLUSIONS: This machine learning and ensemble approach can make accurate, real-time influenza-like illness forecasts for a 4-week period, and thus, facilitate decision making.

Severe diabetes complications among patients with diabetes with regular follow-up: Does care setting matter?

OBJECTIVE: To investigate diabetes outcomes by long-term trajectories of patients' care settings among diabetes patients with regular follow-up. RESEARCH DESIGN AND METHODS: This longitudinal population-based cohort study used data from the National Health Insurance Research Database in Taiwan. The trajectories of diabetes care-seeking behaviours among newly diagnosed diabetes patients with regular follow-up were identified using a group-based trajectory model from 2000 to 2004. Severe diabetes complications were assessed for the period 2005-2010. Cox-proportional hazard method with a cumulative incidence function was applied. RESULTS: Among the diabetes patients with regular follow-up during the first 5 years since diagnosis, 44.5% and 40.6% were persistently cared for in generalized care settings and specialized settings, respectively. Only 14.9% of them had shifted between different levels of care setting during the first 5 years. No significant difference in adverse outcomes was observed between patients who were persistently treated in generalized and specialized care settings. Significantly worse outcomes were observed among patients who shifted from generalized care settings to specialized settings (adjusted hazard ratio [aHR]=3.2, 95% confidence interval [CI]: 1.5, 6.8). In contrast, among the elderly, regular users of generalized care providers had a higher hazard of adverse outcomes than those of specialized care providers (aHR = 3.3, 95% CI: 1.0, 10.7). CONCLUSIONS: Diabetes patients who were persistently treated in generalized care settings had health outcomes comparable to those who were persistently treated in specialized care settings. However, for elderly and less stable patients, regular diabetes care in specialized care settings was preferable.

Plasma lipid concentrations and survival in geriatric population: A retrospective cohort study.

Plasma lipids in mid-life are important predictors for cardiovascular events and deaths. However, the association between plasma lipid concentrations and mortality in late life is controversial. Recent studies showed that older people with extremely low total cholesterol (TC) have poor survival outcome, but this conclusion was drawn mostly from Western cohorts. Our study investigated association between plasma lipid concentrations and mortality in Taiwanese elderly population.A retrospective cohort study was conducted among the 69,824 elderly people who participated in the Taipei City Geriatric Health Examination between 2006 and 2010, with a mean follow-up of 3.6 years. The measurements of TC, high density lipoprotein (HDL) and triglycerides were obtained from the records of the participants. Low density lipoprotein (LDL) was calculated using Friedewald formula in 69,088 participants. All lipid components were categorized into quartiles. Males and females were analyzed separately using multivariate Cox proportional hazards models.The elderly with the lowest quartile of TC (<175 mg/dL), HDL cholesterol (<43 mg/dL) and LDL cholesterol (<100.4 mg/dL) were at higher risk of all-cause mortality. Older females with the lowest quartile of TC and LDL cholesterol had higher cardiovascular mortality. Older females with the lowest quartile of HDL had higher mortality from cardiovascular and cerebrovascular diseases.We concluded that TC, mostly attributed to LDL cholesterol, was inversely related to all-cause mortality. HDL remained to be protective against both cardiovascular and stroke mortality in older females. The target levels of plasma lipids in people older than 65 years should be different from that in younger adults.

Investigating the relationships among lung function variables in chronic obstructive pulmonary disease in men.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the independent contributions of individual lung function variables to outcomes may be lower when they are modelled together if they are collinear. In addition, lung volume measurements may not be necessary after spirometry data have been obtained. However, these hypotheses depend on whether forced vital capacity (FVC) can predict total lung capacity (TLC). Moreover, the definitions of hyperinflation and air trapping according to lung function variables overlap and need be clarified. Therefore, the aim of this study was to evaluate the relationships among various lung function parameters to elucidate these issues. METHODS: Demographic data and 26 parameters of full lung function were measured in 94 men with COPD and analyzed using factor and correlation analyses. RESULTS: Factor analysis revealed five latent factors. Inspiratory capacity (IC)/TLC and residual volume (RV)/TLC were most strongly correlated with all other lung volumes. IC/TLC, RV/TLC, and functional residual capacity (FRC)/TLC were collinear and were potential markers of air trapping, whereas TLC%, FRC%, and RV% were collinear and were potential markers of hyperinflation. RV/TLC >0.4 (or IC/TLC <0.4) was comparable with the ratio of forced expiratory volume in one second (FEV1) and FVC <0.7. FVC% and FEV1% were poorly correlated with TLC%. The correlation study showed that TLC%, RV/TLC, and FEV1% could be used to represent individual latent factors for hyperinflation, air trapping, inspiration, expiration, and obstruction. Combined with diffusion capacity%, these four factors could be used to represent comprehensive lung function. CONCLUSIONS: This study identified collinear relationships among individual lung function variables and thus selecting variables with close relationships for correlation studies should be performed with caution. This study also differentiated variables for air trapping and lung hyperinflation. Lung volume measurements are still required even when spirometry data are available. Four out of 26 lung function variables from individual latent factors could be used to concisely represent lung function.

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.

Variation in the 11-year trajectories of medical care seeking behaviors in diabetes patients under a single payer system: persisting gaps to be filled.

BACKGROUND: Care-seeking behavior is widely acknowledged to have strong influences on health outcomes among individuals with chronic conditions including diabetes. Despite its dynamic nature, care seeking behavior are often considered as time invariant in most studies. The likelihood of patients changing their regularity and source of chronic care over time is often neglected. This study aimed to determine the long-term trajectories of care-seeking patterns of both care-seeking regularity and health provider choices; and their associated factors among patients with type 2 diabetes under the National Health Insurance (NHI) program in Taiwan. METHODS: We utilized population-based data from the National Health Insurance Research Database (NHIRD) in Taiwan. Three thousand, nine hundred and eighty-seven adult patients with newly diagnosed type 2 diabetes in 1999 were enrolled in the cohort. We assessed their trajectories of regular care visits and sources of diabetes care from 2000 to 2010. A group-based trajectory model was applied. RESULTS: Seven distinct groups of long-term care-seeking patterns were identified. Only 51.44% of patients with newly diagnosed diabetes had regularly visited their providers over time. Among them, 56.41 and 16.09% had persistently sought care from generalized and specialized providers, respectively. 27.50% had sought care from different levels of providers. Patients who were male, elderly, low-income, and had a higher baseline diabetes severity were significantly more likely to either continue with their irregular care-seeking behavior or fail to maintain their regular care seeking behavior over time. Those who were younger, had a higher socioeconomic status, and lived in an urban area were significantly more likely to persistently seek care from specialized care settings. CONCLUSIONS: This study is the first population-based assessment of long-term care-seeking behaviors of type 2 diabetes patients under a single-payer system with a comprehensive benefit coverage. The most alarming finding was that, despite the existence of the comprehensive universal health insurance coverage in Taiwan, almost 50% of patients did not seek or maintain regular visits to providers over time as recommended. Understanding variations in the long-term trajectories of care adherence and sources of care may help to identify gaps in diabetes care management.

Development and Validation of a New Short-Form Health Literacy Instrument (HLS-SF12) for the General Public in Six Asian Countries.

BACKGROUND: No comprehensive short-form health literacy (HL) survey tool has been available for general use across Asia. OBJECTIVE: This study aimed to develop and validate a short-form HL instrument derived from the 47-item European Health Literacy Questionnaire (HLS-EU-Q47). METHODS: A population survey (N = 10,024) was conducted from 2013 to 2015 using the HLS-EU-Q47 in 1,029 participants from Indonesia, 1,845 from Kazakhstan, 462 from Malaysia, 1,600 from Myanmar, 3,015 from Taiwan, and 2,073 from Vietnam. Validation of the short form was evaluated by principle component analysis, internal consistency, Pearson correlation, and regression analysis. KEY RESULTS: Based on responses from six countries, a 12-item short-form HL questionnaire (HLS-SF12) was developed, retaining the conceptual framework of the HLS-EU-Q47 and accounting for the high variance of the full-form (i.e., 90% in Indonesia, 91% in Myanmar, 93% in Malaysia, 94% in Taiwan, and 95% in both Kazakhstan and Vietnam). The HLS-SF12 was demonstrated to have adequate psychometric properties, including high reliability (Cronbach's alpha = .85), good criterion-related validity, a moderate and high level of item-scale convergent validity, no floor or ceiling effect, and good model-data-fit throughout the populations in these countries. CONCLUSIONS: The HLS-SF12 was shown to be a valid and reliable tool for HL surveys in the general public in six Asian countries. [HLRP: Health Literacy Research and Practice. 2019;3(2):e90-e102.]. PLAIN LANGUAGE SUMMARY: A health literacy survey was conducted from 2013 to 2015 in six Asian countries using the European Health Literacy Questionnaire (HLS-EU-Q47). The collected data were used to develop and validate a comprehensive short-form questionnaire. A health literacy questionnaire with 12 items (HLS-SF12) that retains the original conceptual framework of the HLS-EU-Q47 was demonstrated to be reliable and valid.

Developing a New Marker of Dynamic Hyperinflation in Patients with Obstructive Airway Disease - an observational study.

Tidal volume at peak exercise and vital capacity ratio (VTpeak/VC) and VTpeak/inspiratory capacity (IC) were used to differentiate lung expansion in subjects with normal health and chronic obstructive pulmonary disease (COPD) from that in subjects with restrictive ventilation. However, VC and IC variably change due to pseudorestriction of lung volumes. Thus, these variables are currently not recommended. In contrast, total lung capacity (TLC) does little change during exercise. The aims of the study investigated whether VTpeak/TLC is more significantly correlated with static air trapping and lung hyperinflation in patients with COPD than VTpeak/IC, VTpeak/FVC, and VTpeak/SVC (study 1), and developed a marker to replace dynamic IC maneuvers by evaluation of the relationship between end-expiratory lung volume (EELV) and VTpeak/TLC and identification of a cutoff value for VTpeak/TLC (study 2). One hundred adults with COPD (study 1) and 23 with COPD and 19 controls (study 2) were analyzed. Spirometry, lung volume, diffusing capacity, incremental cardiopulmonary exercise tests with dynamic IC maneuvers were compared between groups. An ROC curve was generated to identify a cut off value for VTpeak/TLC. In study 1, VTpeak/TLC was more significantly associated with airflow obstruction, static air trapping and hyperinflation. In study 2, VTpeak/TLC was highly correlated with EELV in the patients (r = -0.83), and VTpeak/TLC ≥ 0.27 predicted that 18% of the patients with static air trapping and hyperinflation can expand their VT equivalent to the controls. In conclusions, VTpeak/TLC was superior to other VTpeak/capacities. VTpeak/TLC may be a marker of dynamic hyperinflation in subjects with COPD, thereby avoiding the need for dynamic IC maneuvers. VTpeak/TLC < 0.27 identified approximately 82% of subjects with COPD who could not adequately expand their tidal volume. As most of our participants were male, further studies are required to elucidate whether the results of this study can be applied to female patients with COPD.

Plasma MCP-1 and Cognitive Decline in Patients with Alzheimer's Disease and Mild Cognitive Impairment: A Two-year Follow-up Study.

Monocyte chemoattractant protein-1 (MCP-1, also known as chemokine CCL2) is a vital chemokine that mediates inflammation in Alzheimer's disease (AD). We analyzed the associations between the baseline plasma MCP-1 level, longitudinal cognitive changes, and genetic effects of CCL2 rs1024611 and its receptor, CC-chemokine receptor 2 (CCR2) rs1799864, in AD. In total, 310 AD patients and 66 mild cognitive impairment (MCI) patients were followed for 2 years, and 120 controls were recruited at baseline for comparison. After adjusting for covariates using one-way analysis of covariance, AD patients had higher plasma MCP-1 levels compared with MCI patients and controls, and severe AD patients had the highest levels. After adjusting for covariates using generalized estimating equation analysis, the results showed that the baseline MCP-1 level was significantly correlated with changes in the two-year Mini-Mental Status Examination (p = 0.046). The A allele of CCR2 rs1799864 was associated with a higher MCP-1 level in AD and MCI patients. In conclusion, plasma MCP-1 might reflect the risk and disease course of AD. A higher plasma MCP-1 level is associated with greater severity and faster cognitive decline. Additionally, the CCR2 polymorphism may play a role in the regulation of MCP-1/CCR2 signaling in AD.