Suppression of the alpha, delta, and omicron variants of SARS-Cov-2 in Taiwan.

BACKGROUND: Taiwan was a coronavirus disease 2019 (COVID-19) outlier, with an extraordinarily long transmission-free record: 253 days without locally transmitted infections while the rest of the world battled wave after wave of infection. The appearance of the alpha variant in May 2021, closely followed by the delta variant, disrupted this transmission-free streak. However, despite low vaccination coverage (<1%), outbreaks were well-controlled. METHODS: This study analyzed the time to border closure and conducted one-sample t test to compare between Taiwan and Non-Taiwan countries prior to vaccine introduction. The study also collected case data to observe the dynamics of omicron transmission. Time-varying reproduction number,Rt, was calculated and was used to reflect infection impact at specified time points and model trends of future incidence. RESULTS: The study analyzed and compare the time to border closure in Taiwan and non-Taiwan countries. The mean times to any border closure from the first domestic case within each country were -21 and 5.98 days, respectively (P < .0001). The Taiwanese government invested in quick and effective contact tracing with a precise quarantine strategy in lieu of a strict lockdown. Residents followed recommendations based on self-discipline and unity. The self-discipline in action is evidenced in Google mobility reports. The central and local governments worked together to enact non-pharmaceutical interventions (NPIs), including universal masking, social distancing, limited unnecessary gatherings, systematic contact tracing, and enhanced quarantine measures. The people cooperated actively with pandemic-prevention regulations, including vaccination and preventive NPIs. CONCLUSIONS: This article describes four key factors underlying Taiwan's success in controlling COVID-19 transmission: quick responses; effective control measures with new technologies and rolling knowledge updates; unity and cooperation among Taiwanese government agencies, private companies and organizations, and individual citizens; and Taiwanese self-discipline.

Beyond the waves: Unraveling pandemic outcomes with genomic insights and immunity analysis - Evidence from 14 countries.

OBJECTIVE: Although the World Health Organization and many governments have recategorized COVID-19 as a generally mild to moderately severe disease, consecutive pandemic waves driven by immune escape variants have underscored the need for timely and accurate prediction of the next outbreak. Nevertheless, little attention has been paid to translating genomic data and infection- and vaccine-induced immunity into direct estimates. METHODS: We retrieved epidemiologic and genomic data shortly before pandemic waves across 14 developed countries from late 2021 to mid-2022 and examined associations between early-stage variant competition, infection- and vaccine-induced immunity, and the time intervals between wave peaks. We applied regression analysis and the generalized estimating equation method to construct an inferential model. RESULTS: Each per cent increase in the proportion of a new variant was associated with a 1.0% reduction in interpeak intervals on average. Curvilinear associations between vaccine-induced immunity and outcome variables were observed, suggesting that reaching a critical vaccine distribution rate may decrease the caseload of the upcoming wave. CONCLUSIONS: By leveraging readily accessible pre-outbreak genomic and epidemiologic data, our results not only substantiate the predictive potential of early variant fractions but also propose that immunity acquired through infection alone may not sufficiently mitigate transmission. Conversely, a rapid and widespread vaccination initiative appears to be correlated with a decrease in disease incidence.

Interregional mobility in different age groups is associated with COVID-19 transmission in the Taipei metropolitan area, Taiwan.

Before vaccines were introduced, mobility restriction was one of the primary control measures in the early stage of the coronavirus disease 2019 (COVID-19) pandemic. Because different age groups face disproportionate health risks, differences in their mobility changes affect the effectiveness of pandemic control measures. This study aimed to investigate the relationship between multiscale mobility patterns in different age groups and COVID-19 transmission before and after control measures implementation. Data on daily confirmed case numbers, anonymized mobile phone data, and 38 socioeconomic factors were used to construct negative binomial regression models of these relationships in the Taipei metropolitan area in May 2021. To avoid overfitting, the socioeconomic factor dimensions were reduced by principal component analysis. The results showed that inter-district mobility was a greater promoter of COVID-19 transmission than was intra-district mobility (coefficients: pre-alert, 0.52 and 0.43; post-alert, 0.41 and 0.36, respectively). Moreover, both the inter-district mobility of people aged 15-59 and ≥ 60 years were significantly related to the number of confirmed cases (coefficients: pre-alert, 0.82 and 1.05; post-alert, 0.48 and 0.66, respectively). The results can help agencies worldwide formulate public health responses to emerging infectious diseases.

Real-time forecasting of COVID-19 spread according to protective behavior and vaccination: autoregressive integrated moving average models.

BACKGROUND: Mathematical and statistical models are used to predict trends in epidemic spread and determine the effectiveness of control measures. Automatic regressive integrated moving average (ARIMA) models are used for time-series forecasting, but only few models of the 2019 coronavirus disease (COVID-19) pandemic have incorporated protective behaviors or vaccination, known to be effective for pandemic control. METHODS: To improve the accuracy of prediction, we applied newly developed ARIMA models with predictors (mask wearing, avoiding going out, and vaccination) to forecast weekly COVID-19 case growth rates in Canada, France, Italy, and Israel between January 2021 and March 2022. The open-source data was sourced from the YouGov survey and Our World in Data. Prediction performance was evaluated using the root mean square error (RMSE) and the corrected Akaike information criterion (AICc). RESULTS: A model with mask wearing and vaccination variables performed best for the pandemic period in which the Alpha and Delta viral variants were predominant (before November 2021). A model using only past case growth rates as autoregressive predictors performed best for the Omicron period (after December 2021). The models suggested that protective behaviors and vaccination are associated with the reduction of COVID-19 case growth rates, with booster vaccine coverage playing a particularly vital role during the Omicron period. For example, each unit increase in mask wearing and avoiding going out significantly reduced the case growth rate during the Alpha/Delta period in Canada (-0.81 and -0.54, respectively; both p < 0.05). In the Omicron period, each unit increase in the number of booster doses resulted in a significant reduction of the case growth rate in Canada (-0.03), Israel (-0.12), Italy (-0.02), and France (-0.03); all p < 0.05. CONCLUSIONS: The key findings of this study are incorporating behavior and vaccination as predictors led to accurate predictions and highlighted their significant role in controlling the pandemic. These models are easily interpretable and can be embedded in a "real-time" schedule with weekly data updates. They can support timely decision making about policies to control dynamically changing epidemics.

Screening and identification of emodin as an EBV DNase inhibitor to prevent its biological functions.

BACKGROUND: The Epstein-Barr virus (EBV) is a prevalent oncovirus associated with a variety of human illnesses. BGLF5, an EBV DNase with alkaline nuclease (AN) activity, plays important roles in the viral life cycle and progression of human malignancies and has been suggested as a possible diagnostic marker and target for cancer therapy. Methods used conventionally for the detection of AN activity, radioactivity-based nuclease activity assay and DNA digestion detection by gel electrophoresis, are not suitable for screening AN inhibitors; the former approach is unsafe, and the latter is complicated. In the present study, a fluorescence-based nuclease activity assay was used to screen several natural compounds and identify an EBV DNase inhibitor. RESULTS: Fluorescence-based nuclease activity assays, in which the DNA substrate is labelled with PicoGreen dye, are cheaper, safer, and easier to perform. Herein, the results of the fluorescence-based nuclease activity assay were consistent with the results of the two conventional methods. In addition, the PicoGreen-labelling method was applied for the biochemical characterisation of viral nucleases. Using this approach, we explored EBV DNase inhibitors. After several rounds of screening, emodin, an anthraquinone derivative, was found to possess significant anti-EBV DNase activity. We verified the efficacy of emodin using the conventional DNA-cleavage assay. Furthermore, using comet assay and micronucleus formation detection, we confirmed that emodin can inhibit DNase-induced DNA damage and genomic instability. Additionally, emodin treatment inhibited EBV production. CONCLUSIONS: Using a PicoGreen-mediated nuclease activity assay, we successfully demonstrated that emodin has the potential to inhibit EBV DNase nuclease activity. Emodin also inhibits EBV DNase-related biological functions, suggesting that it is a potential inhibitor of EBV DNase.

Mechanical transmission of dengue virus by Aedes aegypti may influence disease transmission dynamics during outbreaks.

BACKGROUND: Dengue virus outbreaks are increasing in number and severity worldwide. Viral transmission is assumed to require a minimum time period of viral replication within the mosquito midgut. It is unknown if alternative transmission periods not requiring replication are possible. METHODS: We used a mouse model of dengue virus transmission to investigate the potential of mechanical transmission of dengue virus. We investigated minimal viral titres necessary for development of symptoms in bitten mice and used resulting parameters to inform a new model of dengue virus transmission within a susceptible population. FINDINGS: Naïve mice bitten by mosquitoes immediately after they took partial blood meals from dengue infected mice showed symptoms of dengue virus, followed by mortality. Incorporation of mechanical transmission into mathematical models of dengue virus transmission suggest that this supplemental transmission route could result in larger outbreaks which peak sooner. INTERPRETATION: The potential of dengue transmission routes independent of midgut viral replication has implications for vector control strategies that target mosquito lifespan and suggest the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes. FUNDING: This study was funded by grants from the National Health Research Institutes, Taiwan (04D2-MMMOST02), the Human Frontier Science Program (RGP0033/2021), the National Institutes of Health (1R01AI143698-01A1, R01AI151004 and DP2AI152071) and the Ministry of Science and Technology, Taiwan (MOST104-2321-B-400-016).

Comparison the acute toxicity of two different induction chemotherapy schedules with cisplatin and fluorouracil in nasopharyngeal carcinoma patients.

PURPOSE: To compare the acute toxicity of two different induction chemotherapy (IndCT) regimen followed by the same IMRT in patients with advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From July 2015 to December 2016, 110 NPC patients with stage III-IV diseases were prospectively randomized to receive either a conventional triweekly cisplatin + 5-fluorouracil (PF) for 3 cycles or weekly P-F for 10 doses, followed by the same IMRT to both arms. The primary endpoints of this study were grade 3/4 and any grade acute toxicities during IndCT period. The secondary endpoints included tumor response and various survivals. RESULTS: Baseline patient characteristics were comparable in both groups. Patients who received weekly P-F experienced significant reduction of grade 3/4 acute toxicities, including neutropenia (12.7% vs. 40.0%, P = 0.0012), anorexia (0% vs. 14.6%, P = 0.0059), mucositis (0% vs. 14.6%, P = 0.0059), and hyponatremia (0% vs. 16.4%, P = 0.0027), compared with the triweekly PF group, resulting in fewer IndCT interruptions (1.8% vs. 16.4%, P = 0.0203), emergency room visits (0% vs. 12.7%, P = 0.0128), and additional hospitalizations (0% vs. 9.1%, P = 0.0568). The acute toxicities during IMRT period were similar. Weekly P-F arm had higher complete response rates (83.6% vs. 61.8%, P = 0.0152) and lower relapse rates (16.4% vs. 33.3%, P = 0.0402) after a median follow-up of 67 months. Kaplan-Meier survival analyses revealed a better trend of locoregional failure-free (P = 0.0892), distant metastasis failure-free (P = 0.0775), and progression-free (P = 0.0709) survivals, favoring the weekly P-F arm. CONCLUSION: IndCT of weekly schedule does reduce acute toxicities without compromised tumor response and survivals.

Internet searches for "insomnia" and "suicide" mediated by stay-at-home behaviors in 45 countries during the first 12 months of the COVID-19 pandemic.

BACKGROUND: This study aimed to investigate (1) the mental health impacts (i.e., insomnia and suicide ideas) of the COVID-19 pandemic and (2) the mediation effects of stay-at-home levels on those impacts. METHODS: This study investigated monthly national COVID-19 deaths, stay-at-home levels, and internet searches for words for "insomnia" and "suicide" across 45 countries during the first year of the COVID-19 pandemic (March 1, 2020, to February 28, 2021). We used the changes of internet search volumes for "insomnia" and "suicide" (from the Google Trends database) to represent the mental health impacts, and the time of cell phone activity at the residence (from Google Location History) to estimate the stay-at-home effects. We computed the proportion mediated (PM) caused by stay-at-home levels in the COVID-19 impacts on insomnia and suicide ideas, respectively. RESULTS: Throughout the first year of the COVID-19 pandemic, national COVID-19 deaths significantly correlated to increased internet searches for "insomnia" but decreased searches for "suicide". In addition, the mediation effect was significant in the first six-month of COVID-19-related increases in insomnia (PM = 42.6 %, p = 0.016), but this effect was not significant (PM = 13.1 %, p = 0.270) in the second six-month. By contrast, the mediation effect was not significant in the first six-month of COVID-19-related decrease in suicide ideation (PM = 8.1 %, p = 0.180), but this effect was significant (PM = 39.6 %, p = 0.014) in the second six-month. CONCLUSIONS: Stay-at-home levels significantly mediated both increased insomnia and decreased suicide ideas, but within different time frames.

Distinct Immunogenetic Profiles of Chronic Lymphocytic Leukemia in Asia: A Taiwan Cooperative Oncology Group Registry Study.

Asian patientswith chronic lymphocytic leukemia (CLL) exhibit immunoglobulin heavy variable (IGHV) gene repertoires that are distinct from those observed in Western populations, and a higher proportion of Asian CLL patients carry heavy loads of somatic hypermutations (SHM) within the B-cell receptor immunoglobulins (BcR IG). Due to the low regional incidence of CLL in Asia, only a limited number of studies had attempted to probe the phenomenon of BcR IG stereotypy in Asian populations. In this study, we analyzed the IGHV-IGHD-IGHJ gene rearrangements from a series of 255 CLL patients recruited in a nationwide, multicenter study in Taiwan. Our analysis revealed that the IGHV gene repertoire was characterized by evident biases, with IGHV3-7, IGHV4-34, and IGHV3-23 being the most frequent rearranged IGHV genes, and a higher proportion of cases carrying mutated IGHV. In terms of BcR stereotypy, the incidence of major subsets was less frequent in this cohort, with subsets #77 and #28A being the most common, while the incidence of minor subsets was approximately equivalent to that reported in the Western cohorts. With this study, we provide evidence that CLL in Asia is indeed associated with distinct immunogenetic characteristics regarding IGHV gene usage, SHM status, and BcR IG stereotypy.

Contribution of Testing Strategies and Contact Tracing towards COVID-19 Outbreaks Control: A Mathematical Modeling Study.

This modeling study considers different screening strategies, contact tracing, and the severity of novel epidemic outbreaks for various population sizes, providing insight into multinational containment effectiveness of emerging infectious diseases, prior to vaccines development. During the period of the ancestral SARS-Cov-2 virus, contact tracing alone is insufficient to achieve outbreak control. Although universal testing is proposed in multiple nations, its effectiveness accompanied by other measures is rarely examined. Our research investigates the necessity of universal testing when contact tracing and symptomatic screening measures are implemented. We used a stochastic transmission model to simulate COVID-19 transmission, evaluating containment strategies via contact tracing, one-time high risk symptomatic testing, and universal testing. Despite universal testing having the potential to identify subclinical cases, which is crucial for non-pharmaceutical interventions, our model suggests that universal testing only reduces the total number of cases by 0.0009% for countries with low COVID-19 prevalence and 0.025% for countries with high COVID-19 prevalence when rigorous contact tracing and symptomatic screening are also implemented. These findings highlight the effectiveness of testing strategies and contact tracing in reducing COVID-19 cases by identifying subclinical cases.

A prospective phase II study of biweekly S-1, leucovorin, and gemcitabine in elderly patients with locally advanced or metastatic pancreatic adenocarcinoma - The Taiwan Cooperative Oncology Group T1217 study.

BACKGROUND: Elderly patients with advanced pancreatic adenocarcinoma (APC) are conceived to be frailer and susceptible to treatment toxicity that has led to disparity in lower likelihood of receiving chemotherapy and survival. Optimal chemotherapy is an unmet medical need for elderly patients with APC. PATIENTS AND METHODS: Patients with chemo-naive APC, age ≥70 years, and Eastern Cooperative Oncology Group (ECOG) performance score ≤2 were eligible. The treatment was consisted of biweekly gemcitabine 800 mg/m2, 10 mg/m2/min infusion on day 1 plus oral S-1 and leucovorin (40-60 and 30 mg, respectively) twice daily on days 1-7, the GSL regimen. The primary end-point was progression-free survival with an interested P1 of 5.0 months. RESULTS: Of the 49 enrolled patients, the median age was 76 years, ECOG performance score ≥1 in 59.2%, metastatic diseases in 65.3%, Vulnerable Elders Survey-13 score ≥3 in 71.4%, and Geriatric 8 score ≤14 in 93.9%. After a median 11 cycles of treatment, the overall response rate and disease control rate were 26.5% and 75.5%, respectively. The median progression-free and overall survivals were 6.6 months (95% confidence interval [CI], 5.4-9.2) and 12.5 months (95% CI, 8.9-14.7), respectively. The most common grade 3-4 treatment-related toxicities were anaemia (20.4%), neutropenia (18.4%), and mucositis (12.2%). Patients had improved emotional function and global health status scores during the GSL treatment. CONCLUSION: The study met its primary end-point, which supports further investigation on the merit of GSL in Asian elderly APC patients.

Validation of clinical frailty scale in Chinese translation.

BACKGROUND: Identification of frailty is crucial to guide patient care for the elderly. The Clinical Frailty Scale (CFS) is a reliable, synthesis and clinical judgment-based tool. However, a validated Chinese version of CFS (CFS-C) is lacking. The aim of this study is to describe the translation process of CFS into traditional Chinese and to evaluate its reliability and validity in a geriatric study population in Taiwan. METHODS: This cross-sectional study recruited 221 geriatric outpatients aged 65 years or older at a medical center in Taipei, Taiwan. The Chinese version of CFS was produced following Brislin's translation model. Weighted kappa for agreement and Kendall's tau for correlation were used to assess inter-rater reliability (a subgroup of 52 outpatients) between geriatricians and one research assistant, and validity tests (221 outpatients) by comparing CFS-C with Fried frailty phenotype and Frailty Index based on Comprehensive Geriatric Assessment (FI-CGA). Correlation between CFS-C and other geriatric conditions were also assessed. RESULTS: The inter-rater reliability revealed moderate agreement (weighted kappa = 0.60) and strong correlation (Kendall's tau = 0.67). For criterion validity, CFS-C categorisation showed fair agreement (weighted kappa = 0.37) and significant correlation (Kendall's tau = 0.46) with Fried frailty phenotype, and higher agreement (weighted kappa = 0.51) and correlation (Kendall's tau = 0.63) with FI-CGA categorisation. CFS-C was significantly correlated with various geriatric assessments, including functional disability, physical performance, hand grip, comorbidity, cognition, depression, and nutrition status. No significant correlation was found between CFS-C and appendicular muscle mass. CONCLUSIONS: The CFS-C demonstrated acceptable validity and reliability in Chinese older adults in Taiwan. Development of CFS-C enhanced consistency and accuracy of frailty assessment, both in research and clinical practice.

Discrimination of Methicillin-resistant Staphylococcus aureus by MALDI-TOF Mass Spectrometry with Machine Learning Techniques in Patients with Staphylococcus aureus Bacteremia.

Early administration of proper antibiotics is considered to improve the clinical outcomes of Staphylococcus aureus bacteremia (SAB), but routine clinical antimicrobial susceptibility testing takes an additional 24 h after species identification. Recent studies elucidated matrix-assisted laser desorption/ionization time-of-flight mass spectra to discriminate methicillin-resistant strains (MRSA) or even incorporated with machine learning (ML) techniques. However, no universally applicable mass peaks were revealed, which means that the discrimination model might need to be established or calibrated by local strains' data. Here, a clinically feasible workflow was provided. We collected mass spectra from SAB patients over an 8-month duration and preprocessed by binning with reference peaks. Machine learning models were trained and tested by samples independently of the first six months and the following two months, respectively. The ML models were optimized by genetic algorithm (GA). The accuracy, sensitivity, specificity, and AUC of the independent testing of the best model, i.e., SVM, under the optimal parameters were 87%, 75%, 95%, and 87%, respectively. In summary, almost all resistant results were truly resistant, implying that physicians might escalate antibiotics for MRSA 24 h earlier. This report presents an attainable method for clinical laboratories to build an MRSA model and boost the performance using their local data.

A comprehensive evaluation of COVID-19 policies and outcomes in 50 countries and territories.

The COVID-19 pandemic struck the world unguarded, some places outperformed others in COVID-19 containment. This longitudinal study considered a comparative evaluation of COVID-19 containment across 50 distinctly governed regions between March 2020 and November 2021. Our analysis distinguishes between a pre-vaccine phase (March-November 2020) and a vaccinating phase (December 2020-November 2021). In the first phase, we develop an indicator, termed lockdown efficiency (LE), to estimate the efficacy of measures against monthly case numbers. Nine other indicators were considered, including vaccine-related indicators in the second phase. Linear mixed models are used to explore the relationship between each government policy & hygiene education (GP&HE) indicator and each vital health & socioeconomic (VH&SE) measure. Our ranking shows that surveyed countries in Oceania and Asian outperformed countries in other regions for pandemic containment prior to vaccine development. Their success appears to be associated with non-pharmaceutical interventions, acting early, and adjusting policies as needed. After vaccines have been distributed, maintaining non-pharmacological intervention is the best way to achieve protection from variant viral strains, breakthrough infections, waning vaccine efficacy, and vaccine hesitancy limiting of herd immunity. The findings of the study provide insights into the effectiveness of emerging infectious disease containment policies worldwide.

Maintenance metronomic chemotherapy for metastatic/recurrent nasopharyngeal carcinoma.

BACKGROUND: We investigated the survival impact and toxicity of maintenance metronomic chemotherapy in patients with metastatic/recurrent nasopharyngeal carcinoma (met/rec NPC). METHODS: Ninety-eight patients with met/rec NPC were first salvaged by IV cisplatin-based chemotherapy and showed nonprogression disease; then maintenance metronomic chemotherapy for at least 12 months was recommended. We analyzed the treatment outcome between patients who received (n = 51) and did not receive (n = 47) maintenance chemotherapy. RESULTS: Baseline patient characteristics showed no significant differences between both arms. Median overall survival for patients with and without maintenance chemotherapy was 36.0 and 12.3 months, respectively (p < 0.0001). Similarly, median progression-free survival was 24.7 and 7.3 months, respectively (p < 0.0001). Furthermore, toxicities during maintenance oral chemotherapy period were usually mild. Transient grade 3 leucopenia (9.8%), anemia (3.9%), thrombocytopenia (7.8%), and no grade 4 toxicity were observed. CONCLUSION: After IV salvage chemotherapy, maintenance oral metronomic chemotherapy significantly improved overall and progression-free survivals while demonstrating low toxicity in patients with met/rec NPC.

Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment.

Methadone is a synthetic opioid used for the maintenance treatment (MMT) of heroin dependence. It primarily binds to the µ-opioid receptor (MOR; with its gene, namely OPRM1). Methadone is also an N-methyl-D-aspartate (NMDA) receptor antagonist. The role of NMDA receptor in the regulatory mechanisms of methadone dosage in heroin dependent patients is so far not clear. D-amino acid oxidase (DAO) is an important enzyme that indirectly activates the NMDA receptor through its effect on the D-serine level. To test the hypothesis that genetic polymorphisms in the DAO gene are associated with methadone treatment dose and responses, we selected four single nucleotide polymorphisms (SNPs) in DAO from the literature reports of the Taiwanese population. SNPs were genotyped in 344 MMT patients. In this study, we identified a functional SNP rs55944529 in the DAO gene that reveals a modest but significant association with the methadone dosage in the recessive model of analysis (P = 0.003) and plasma concentrations (P = 0.003) in MMT patients. However, it did not show association with plasma methadone concentration in multiple linear regression analysis. It is also associated with the methadone adverse reactions of dry mouth (P = 0.002), difficulty with urination (P = 0.0003) in the dominant model, and the withdrawal symptoms of yawning (P = 0.005) and gooseflesh skin (P = 0.004) in the recessive model. Our results suggest a role of the indirect regulatory mechanisms of the NMDA reporter, possibly via the DAO genetic variants, in the methadone dose and some adverse reactions in MMT patients.

Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment.

Chronic opioid use disorder patients often also use other substances such as amphetamines. The gene-based analysis method was applied in the genomic database obtained from our previous study with 343 methadone maintenance treatment (MMT) patients. We found that the gene encoding gamma-aminobutyric acid type A receptors (GABA-A receptor) delta subunit isoforms (GABRD) was associated with amphetamine use in heroin dependent patients under MMT in Taiwan. A total of 15% of the 343 MMT patients tested positive for amphetamine in the urine toxicology test. Two genetic variants in the GABRD, rs2889475 and rs2376805, were found to be associated with the positive urine amphetamine test. They are located in the exon 1 of the splice variant and altered amino acid compositions (T126I, C/T, for rs2889475, and R252Q, G/A, for rs2376805). The CC genotype carriers of rs2889475 showed a four times higher risk of amphetamine use than those with TT genotype. The GG genotype carriers of rs2376805 showed a three times higher risk of amphetamine use than the AA genotype carriers. To our knowledge, this is the first report that demonstrated an association of the delta splice variant isoform in the GABA-A receptor with an increased risk of amphetamine use in MMT patients. Our results suggest that rs2889475 and rs2376805 may be indicators for the functional role and risk of amphetamine use in MMT patients.

Nonpolio Enterovirus Activity during the COVID-19 Pandemic, Taiwan, 2020.

In Taiwan, lower nonpolio enterovirus activity during the coronavirus disease pandemic in 2020 compared with 2014-2019 might be attributable to adherence to nonpharmaceutical interventions. The preventable fraction among unexposed persons indicated that 90% of nonpolio enterovirus activity might have been prevented during 2014-2019 by adopting the same measures enforced in 2020.

The effect of preventing subclinical transmission on the containment of COVID-19: Mathematical modeling and experience in Taiwan.

The control strategies preventing subclinical transmission differed among countries. A stochastic transmission model was used to assess the potential effectiveness of control strategies at controlling the COVID-19 outbreak. Three strategies included lack of prevention of subclinical transmission (Strategy A), partial prevention using testing with different accuracy (Strategy B) and complete prevention by isolating all at-risk people (Strategy C, Taiwan policy). The high probability of containing COVID-19 in Strategy C is observed in different scenario, had varied in the number of initial cases (5, 20, and 40), the reproduction number (1.5, 2, 2.5, and 3.5), the proportion of at-risk people being investigated (40%, 60%, 80%, to 90%), the delay from symptom onset to isolation (long and short), and the proportion of transmission that occurred before symptom onset (<1%, 15%, and 30%). Strategy C achieved probability of 80% under advantageous scenario, such as low number of initial cases and high coverage of epidemiological investigation but Strategy B and C rarely achieved that of 60%. Considering the unsatisfactory accuracy of current testing and insufficient resources, isolation of all at-risk people, as adopted in Taiwan, could be an effective alternative.

Real-time dengue forecast for outbreak alerts in Southern Taiwan.

Dengue fever is a viral disease transmitted by mosquitoes. In recent decades, dengue fever has spread throughout the world. In 2014 and 2015, southern Taiwan experienced its most serious dengue outbreak in recent years. Some statistical models have been established in the past, however, these models may not be suitable for predicting huge outbreaks in 2014 and 2015. The control of dengue fever has become the primary task of local health agencies. This study attempts to predict the occurrence of dengue fever in order to achieve the purpose of timely warning. We applied a newly developed autoregressive model (AR model) to assess the association between daily weather variability and daily dengue case number in 2014 and 2015 in Kaohsiung, the largest city in southern Taiwan. This model also contained additional lagged weather predictors, and developed 5-day-ahead and 15-day-ahead predictive models. Our results indicate that numbers of dengue cases in Kaohsiung are associated with humidity and the biting rate (BR). Our model is simple, intuitive and easy to use. The developed model can be embedded in a "real-time" schedule, and the data (at present) can be updated daily or weekly based on the needs of public health workers. In this study, a simple model using only meteorological factors performed well. The proposed real-time forecast model can help health agencies take public health actions to mitigate the influences of the epidemic.