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.

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.

Health-related behaviors moderate the association between age and self-reported health literacy among Taiwanese women.

The role of health-related behaviors in the association between age and health literacy has not been well-elucidated. The present cross-sectional study evaluated the interactions between age and health-related behaviors in 942 women in Taiwan between February and October 2013. Women aged 18-78 years were randomly sampled and recruited from the national administrative system. Self-reported health literacy was measured by the European Health Literacy Survey Questionnaire (HLS-EU-Q47) in Mandarin, asking about sociodemographics and essential health-related behaviors (watching health-related television, community involvement). The interviews were conducted confidentially by well-trained interviewers after having participants' consent. In multiple linear regression models adjusted for education attainment, self-perceived social status, ability to pay for medication, and health-related behaviors, health literacy was significantly negatively related to age (unstandardized regression coefficient, B = -0.04; 95% confidence interval [CI] = (-0.07; 0.00); p = .03). The lower health literacy among older women was significantly modified by watching health-related television programs (from "rarely/not-at-all", B = -0.08 (-0.12, -0.04), p < .001 to "often"; B = 0.10 (0.07, 0.12); p < .001) and community involvement (from "rarely/not-at-all", B = -0.06 (-0.10, -0.03); p = .001 to "often", B = 0.06 (0.03, 0.08); p < .001). Specific health behaviors were protective of older women's health literacy and likely their health.

30 years follow-up and increased risks of breast cancer and leukaemia after long-term low-dose-rate radiation exposure.

BACKGROUND: The current study followed-up site-specific cancer risks in an unique cohort with 30 years' follow-up after long-term low-dose-rate radiation exposure in Taiwan. METHODS: Six thousand two hundred and forty two Taiwanese people received extra exposure in residential and school buildings constructed with Co-60-contaminated steel from 1982 until informed and relocated in early 1990s. The additional doses received have been estimated. During 1983-2012, 300 cancer cases were identified through the national cancer registry in Taiwan, 247 cases with minimum latent periods from initial exposure. The hazard ratios (HR) of site-specific cancers were estimated with additional cumulative exposure estimated individually. RESULTS: Dose-dependent risks were statistically significantly increased for leukaemia excluding chronic lymphocytic leukaemia (HR100mSv 1.18; 90% CI 1.04-1.28), breast cancers (HR100mSv 1.11; 90% CI 1.05-1.20), and all cancers (HR100mSv 1.05; 90% CI 1.0-1.08, P=0.04). Women with an initial age of exposure lower than 20 were shown with dose response increase in breast cancers risks (HR100mSv 1.38; 90% CI 1.14-1.60; P=0.0008). CONCLUSIONS: Radiation exposure before age 20 was associated with a significantly increased risk of breast cancer at much lower radiation exposure than observed previously.

Effort-reward imbalance and self-rated health among Gambian healthcare professionals.

BACKGROUND: The effort-reward imbalance (ERI) model of work stress has been widely applied in investigating association between psychosocial factors at work and health. This study examined associations between perceived psychosocial work stress as measured by the ERI model and self-rated health (SRH) among nurses and environmental health officers (EHOs) working in secondary public healthcare facilities in the Gambia. METHOD: A cross-sectional study on a random sample of 287 health care professionals (201 nurses and 86 EHOs). A 22-item ERI questionnaire was used to collect data on the psychosocial factors defined by the ERI model. SRH was assessed using a single item measure. RESULTS: The distribution of subjective health was not statistically different between nurses and EHOs. However, our study uncovered significant associations between perceived psychosocial work stress and subjective health. Specifically, we found that a perceived high effort-reward imbalance (ER-ratio > 1) is a significant risk factor for poor SRH, in both occupational groups. However, over-commitment was not significantly associated with poor SRH in the two groups. When efforts and rewards were considered as separate variables in the analysis, rewards were inversely associated with poor SRH in both groups. CONCLUSION: Because of the high perceived Effort-Reward Imbalance among healthcare professionals at secondary public healthcare facilities, it is necessary to modify working conditions through improvement of psychosocial work environment, such as reasonable allocation of resources to increase pay, incentives or other forms of rewards from government. Interventions that could mitigate and prevent stress at work are worth considering in future healthcare policies.

The serologic decoy receptor 3 (DcR3) levels are associated with slower disease progression in HIV-1/AIDS patients.

BACKGROUND/PURPOSE: The decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor (TNFR) super-family. It counteracts the biological effects of Fas ligands and inhibits apoptosis. The goals of this study were to understand the associations between serologic DcR3 (sDcR3) levels and different human immunodeficiency virus type 1 (HIV-1) subtypes, as well as the AIDS disease progression. METHODS: Serum samples from 61 HIV/AIDS patients, who had been followed up every 6 months for 3 years, were collected. sDcR3 levels were quantified using an enzyme immunoassay (EIA). RESULTS: The sDcR3 levels in patients with HIV-1 subtype B were significantly higher than those in patients infected with subtype CRF01_AE (p < 0.001). In addition, multivariable linear mixed model analysis demonstrated that HIV-1 subtype B and slow disease progression were associated with higher levels of sDcR3, adjusting for potential predictors (p = 0.0008 and 0.0455, respectively). CONCLUSION: HIV-1-infected cells may gain a survival advantage by activating DcR3, which prevents infected cell detection by the host immune system. These data indicate that the sDcR3 level is a biomarker for AIDS disease progression.

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.

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.

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.

Application of loop-mediated isothermal amplification for malaria diagnosis during a follow-up study in São Tomé.

BACKGROUND: A reliable and simple test for the detection of malaria parasite is crucial in providing effective treatment and therapeutic follow-up, especially in malaria elimination programmes. A comparison of four methods, including nested polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) were used for the malaria diagnosis and treatment follow-up in São Tomé and Príncipe, during a successful pre-elimination campaign. METHOD: During the period September to November 2009, blood samples from 128 children (five to 14 years old) with temperature ≥38°C (tympanic) in the District of Agua Grande were examined using four different methods, i.e., histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (HRP-2-RDTs), optical microscopy, nested PCR, and LAMP. First-line treatment with artesunate-amodiaquine was given for uncomplicated malaria and intravenous quinine was given for complicated malaria. Children with persistent positivity for malaria by microscopy, or either by nested PCR, or by LAMP on day 7 were given second-line treatment with artemether-lumefantrine. Treatment follow-up was made weekly, for up to four weeks. RESULTS: On day 0, positive results for HRP-2-RDTs, microscopy, nested PCR, and LAMP, were 68(53%), 47(37%), 64(50%), and 65(51%), respectively. When nested PCR was used as a reference standard, only LAMP was comparable; both HRP-2-RDTs and microscopy had moderate sensitivity; HRP-2-RDTs had poor positive predictive value (PPV) and a moderate negative predictive value (NPV) for the treatment follow-up. Seventy-one children with uncomplicated malaria and eight children with complicated falciparum malaria were diagnosed based on at least one positive result from the four tests as well as clinical criteria. Twelve of the 79 children receiving first-line treatment had positive results by nested PCR on day 7 (nested PCR-corrected day 7 cure rate was 85%). After the second-line treatment, nested PCR/LAMP-corrected day 28 cure rate was 83% for these 12 children. CONCLUSIONS: HRP-2-RDTs have similar sensitivity as microscopy but less specificity. However, as compared to nested PCR, the poor sensitivity of HRP-2-RDTs indicates that low parasitaemia may not be detected after treatment, as well as the low specificity of HRP-2-RDTs indicates it cannot be applied for treatment follow-up. LAMP has similar sensitivity and specificity to nested PCR. With high PPV and NPV, LAMP is simpler and faster as compared to nested PCR with the advantage of detecting low parasitaemia becoming a potential point-of-care test for treatment follow-up.

Cardiovascular determinants of prognosis in normotensive hemodialysis patients.

BACKGROUND: Normotension has been hold to be the goal of hemodialysis. It remains obscure which cardiovascular parameter determines the prognosis in these normotensive hemodialysis patients. METHODS: We prospectively enrolled 145 hemodialysis patients, who had attained normotension without anti-hypertensive medications, and followed them for 72.6 ± 28.5 months. Important cardiovascular parameters were obtained at enrollment. Predictors for all-cause and cardiovascular mortalities were identified with the Cox model. RESULTS: There were 45 (18 cardiovascular/27 non-cardiovascular) deaths occurred during follow-up. Age, diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), carotid intima-media thickness (CIMT), and aortic pulse wave velocity (PWV) were significant predictors for all-cause and cardiovascular mortalities. After adjustment for age and diabetes, only LVEF was significantly associated with all-cause mortality. LVEF was significantly associated with cardiovascular mortality. LVEF remained as a significant independent predictor of cardiovascular death after adjusting for age, diabetes, LVMI, CIMT, or PWV, respectively. CONCLUSION: LVEF is the independent predictor for all-cause and cardiovascular mortalities in the normotensive hemodialysis patients.

Using statistical techniques to predict dynamic arterial P(CO(2)) in patients with COPD during maximum exercise.

BACKGROUND: P(aCO(2)) as measured during exercise in patients with COPD is poorly predicted (predicted P(aCO(2))) from lung function testing and some noninvasive measurements, such as end-tidal P(CO(2)) (P(ETCO(2))). OBJECTIVE: We performed a number of statistical techniques on P(ETCO(2)) and its interaction with other physiologic variables during exercise testing, in order to improve our ability to predict P(aCO(2)). The estimated P(aCO(2)) as determined from these techniques may therefore be used to contrast the P(ETCO(2)) readings that are measured during an incremental exercise test on a breath-by-breath basis (ie, P(aCO(2)) - P(ETCO(2))), and to identify exercise-induced hypercapnia. METHODS: Forty-seven men with COPD underwent both pulmonary function testing and incremental exercise testing until limited by symptoms. Arterial blood gases and exercise physiological measurements were performed during maximal exercise testing. The prediction equations for P(aCO(2)) were generated using regression techniques with the leave-one-out cross-validation technique. RESULTS: Forty-one patients were included in the final analysis after 6 patients were excluded due to inadequate data collection. The best prediction equation we found was: predicted P(aCO(2)) = 23.71 + P(ETCO(2)) × (0.9-0.01 × D(LCO) -0.04 × V(T)) - 2.61 × SVC - 0.04 × MEP, where D(LCO) is diffusing capacity for carbon monoxide in mL/min/mm Hg, V(T) is tidal volume in L, SVC is slow vital capacity in L, and MEP is maximum expiratory pressure in cm H(2)O. The difference between the measured and predicted P(aCO(2)) at each time point was not statistically significant (all P > .05). The standard errors of the estimated P(aCO(2)) at each time point were 0.91-1.12 mm Hg. CONCLUSIONS: A validated mixed-model regression derived equation yields a predicted P(aCO(2)) trend during exercise that can be helpful when interpreting exercise testing to determine P(aCO(2)) - P(ETCO(2)) and exercise-induced hypercapnia.

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.

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.

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.

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.

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.