Maternal outcomes in association with motor vehicle crashes during pregnancy: a nationwide population-based retrospective study.

BACKGROUND: Limited studies have assessed the association of motor vehicle crashes (MVCs) during pregnancy with adverse maternal outcomes using a population-based nationwide dataset that covers all MVCs. METHODS: A total of 20 844 births from women who had been involved in MVCs during pregnancy were obtained from the National Birth Notification (BN) Database in Taiwan. We randomly selected 83 274 control births from women in the BN matched on age, gestational age and crash date. All study subjects were linked to medical claims and the Death Registry to identify the maternal outcomes after crashes. Conditional logistic regression models were used to estimate the adjusted odds ratio (aOR) and 95% CI of adverse outcomes associated with MVCs during pregnancy. RESULTS: Pregnant women involved in MVCs had significantly higher risks of placental abruption (aOR=1.51, 95% CI 1.30 to 1.74), prolonged uterine contractions (aOR=1.31, 95% CI 1.11 to 1.53), antepartum haemorrhage (aOR=1.19, 95% CI 1.12 to 1.26) and caesarean delivery (aOR=1.05, 95% CI 1.02 to 1.09) than the controls. Such elevated risks tended to be higher in the MVCs with greater severity. Scooter riders had higher ORs of various adverse maternal outcomes than car drivers. CONCLUSIONS: Women involved in MVCs during pregnancy were at increased risk of various adverse maternal outcomes, especially in those with severe MVCs and riding scooters at MVCs. These findings suggest that clinicians should be aware of these effects, and educational materials that include the above information should be provided as part of prenatal care.

Pregnancy is associated with more severe injuries from motor vehicle crashes.

OBJECTIVE: Whether pregnancy is associated with severe injuries from motor vehicle crashes (MVCs) remains unclear. This study aimed to investigate the potential relationship between pregnancy and severity of injuries from MVCs. METHODS: We identified a total of 23,559 pregnant women victims who encountered MVCs during pregnancy as well as 94,236 age- and calendar year-at MVC matched non-pregnant women victims that are also involved in MVCs. Injury severity was assessed using the Maximum Abbreviated Injury Scale (MAIS) based on the diagnosis of medical claims after MVCs. Multinomial logistic regression models were used to estimate the odds ratio and corresponding 95 % CI of injury severity levels associated with pregnancy. RESULTS: Pregnant women had a significantly higher risk of both severe (adjusted odds ratio, aOR = 1.79, 95 % CI = 1.54-2.08) and mild injuries (aOR = 8.63, 95 % CI = 8.21-9.07) following MVCs as compared to non-pregnant women victims. Particularly, pregnant women who were riding scooters had an increased risk of severe injury (aOR = 4.25, 95 % CI = 3.58-5.04). In addition, pregnant women who experienced MVC but without any injury were more likely to visit a clinic than non-pregnant MVC victims. CONCLUSION: Pregnant women victims, particularly those who were riding scooters involved in MVCs suffered from a higher risk of severe injury as compared to their non-pregnant counterparts. Our findings suggest that women should consider avoiding riding a scooter and must use restrictive devices during pregnancy, which would help reduce the severity of injuries sustained following an MVC.

Integrating domain knowledge with machine learning to detect obstructive sleep apnea: Snore as a significant bio-feature.

Our study's main purpose is to emphasise the significance of medical knowledge of pathophysiology before machine learning. We investigated whether combining domain knowledge with machine learning results might increase accuracy and minimise the number of bio-features used to detect obstructive sleep apnea (OSA). The present study analysed data on 36 self-reported symptoms and 24 clinical features obtained from 3,495 patients receiving polysomnography at a regional hospital and a medical centre. The area under the receiver operating characteristic (AUC) curve was used to evaluate patients with and without moderate or severe OSA using three prediction models on the basis of various estimation methods: the multiple logistic regression (MLR), support vector machine (SVM), and neural network (NN) methods. Odds ratios stratified by gender and age were also measured to account for clinicians' common sense. We discovered that adding the self-reported snoring item improved the AUC by 0.01-0.10 and helped us to rapidly achieve the optimum level. The performance of four items (gender, age, body mass index [BMI], and snoring) was comparable with that of adding two or more items (neck and waist circumference) for predicting moderate to severe OSA (Apnea-Hypopnea Index ≥15 events/hr) in all three prediction models, demonstrating the medical knowledge value of pathophysiology. The four-item test sample AUCs were 0.83, 0.84, and 0.83 for MLR, SVM, and NN, respectively. Participants with regular snoring and a BMI of ≥25 kg/m2 had a greater chance of moderate to severe OSA according to the stratified adjusted odds ratios. Combining domain knowledge into machine learning could increase efficiency and enable primary care physicians to refer for an OSA diagnosis earlier.

Changes in the rankings of leading causes of death in Japan, Korea, and Taiwan from 1998 to 2018: a comparison of three ranking lists.

BACKGROUND: The ranking lists used by most countries for leading causes of death (CODs) comprise broad category such as cancer, heart disease, and accidents. To provide more specific information, the World Health Organization (WHO) and the Institute of Health Metrics and Evaluation (IHME) proposed lists that splitting broad categories into specific categories. We examined the changes in rankings of leading CODs according to different lists in Japan, Korea, and Taiwan from 1998 to 2018. METHODS: We obtained the number of deaths for three countries from the WHO mortality database for 1998, 2008, and 2018. Age-standardized death rates were calculated for rankings 10 leading CODs using WHO 2000 age structure as standard. RESULTS: The first leading COD was cancer in Japan, Korea, and Taiwan from 1998 to 2018 based on government list; nevertheless, became stroke based on WHO list, and was stroke and ischemic heart disease based on IHME list. In the WHO and IHME lists, cancer is categorized based on cancer site. The number of cancer sites included in the 10 leading CODs in 2018 was 4, 4, and 3 in Japan, Korea, and Taiwan, respectively according to the WHO list and was 4, 4, and 2, respectively according to IHME list. The only difference was the rank of liver cancer in Taiwan, which was 6th according to WHO list and was 18th according to IHME list. The ranking and number of deaths for some CODs differed greatly between the WHO and IHME lists due to the reallocation of "garbage codes" into relevant specific COD in IHME list. CONCLUSIONS: Through the use of WHO and the IHME lists, the relative importance of several specific and avoidable causes could be revealed in 10 leading CODs, which could not be discerned if the government lists were used. The information is more relevant for health policy decision making.

Mobilization of Hematopoietic Stem and Progenitor Cells during Dengue Virus Infection.

Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.

Cytokine Signature of Dengue Patients at Different Severity of the Disease.

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

Seroprevalence of Zika and Dengue Virus Antibodies among Migrant Workers, Taiwan, 2017.

A serosurvey of 600 workers newly arrived in Taiwan from 4 Southeast Asia countries showed that 18 (3%) were positive for Zika virus IgM; 6 (1%) fulfilled the World Health Organization criteria for laboratory-confirmed recent Zika virus infection. The incidence of Zika virus infection in Southeast Asia might be underestimated.

Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells.

BACKGROUND: Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. STUDY DESIGN AND METHODS: Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. RESULTS: DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. CONCLUSION: Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.

Low seroprevalence of Zika virus infection among adults in Southern Taiwan.

BACKGROUND: We recently conducted a serosurvey of newly arrived workers in Taiwan from four Southeast Asian countries which revealed that 1% of the migrant workers had laboratory-confirmed recent Zika virus (ZIKV) infection. Taiwan, where Aedes mosquitoes are prevalent, has a close relationship with Southeast Asian countries. Up to now, 21 imported cases of ZIKV infection have been reported in Taiwan, but there has been no confirmed indigenous case. The aim of this serosurvey was to assess whether there was unrecognized ZIKV infections in Taiwan. METHODS: A total of 212 serum samples collected in a cross-sectional seroepidemiologic study conducted during the end of the 2015 dengue epidemic in Tainan, Taiwan, were analyzed. Anti-ZIKV IgM and IgG were tested using commercial enzyme-linked immunosorbent assays (ELISAs). Plaque reduction neutralization tests (PRNTs) for ZIKV and four dengue virus (DENV) serotypes were performed for samples with positive anti-ZIKV antibodies. A confirmed case of ZIKV infection was defined by ZIKV PRNT90 titer ratio ≥ 4 compared to four DENV serotypes. RESULTS: The mean age of the 212 participants was 54.0 years (standard deviation 13.7 years), and female was predominant (67.0%). Anti-ZIKV IgM and IgG were detected in 0 (0%) and 9 (4.2%) of the 212 participants, respectively. For the 9 samples with anti-ZIKV IgG, only 1 sample had 4 times higher ZIKV PRNT90 titers compared to PRNT90 titers against four dengue virus serotypes; this individual denied having traveled abroad. CONCLUSIONS: The results suggest that undetected indigenous ZIKV transmission might have occurred in Taiwan. The findings also suggest that the threat of epidemic transmission of ZIKV in Taiwan does exist due to extremely low-level of herd immunity. Our study also indicates that serological tests for ZIKV-specific IgG remain a big challenge due to cross-reactivity, even in dengue non-endemic countries.

Seroepidemiology of dengue virus infection among adults during the ending phase of a severe dengue epidemic in southern Taiwan, 2015.

BACKGROUND: A severe dengue epidemic occurred in 2015 which resulted in over 22,000 laboratory-confirmed cases. A cross-sectional seroprevalence study was conducted during the ending phase of this epidemic to evaluate the true incidence of dengue virus (DENV) infection and the level of herd immunity. METHODS: Adult residents in three administrative districts with high dengue incidence were recruited; workers in two districts with intermediate dengue incidence were also recruited for comparison. DENV-specific IgM and IgG were tested using commercial enzyme-linked immunosorbent assays. DENV RNA was detected using commercial quantitative real-time reverse transcriptase polymerase chain reaction assay. Univariate and multivariate logistic regressions were performed to identify risk factors for recent and past DENV infection. RESULTS: The overall seroprevalence of anti-DENV IgM and IgG in 1391 participants was 6.8 and 17.4%, respectively. The risk of recent DENV infection increased with age, with the elderly having the highest risk of infection. Living in areas with high incidence of reported dengue cases and having family members being diagnosed with dengue in 2015 were also independent risk factors for recent DENV infection. One sample was found to have asymptomatic viremia with viral load as high as 105 PFU/ml. CONCLUSIONS: Comparing the seroprevalence of anti-DENV IgM with the incidence of reported dengue cases in 2015, we estimated that 1 out of 3.7 dengue infections were reported to the surveillance system; widespread use of rapid diagnostic tests might contribute to this high reporting rate. The results also indicate that the overall herd immunity remains low and the current approved Dengvaxia® is not quite suitable for vaccination in Taiwan.

Impact of the interval between neoadjuvant concurrent chemoradiotherapy and esophagectomy in the modern era: a population-based propensity-score-matched retrospective cohort study in Asia.

BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (nCCRT) is one of the standard-of-care options for locally advanced esophageal squamous cell carcinoma (LA-ESqCC). The optimal interval between nCCRT and esophagectomy is unknown. METHODS: We constructed a propensity-score-matched [1:1 for long (8-12 weeks) vs short (4-7 weeks) intervals] cohort of LA-ESqCC patients who were diagnosed from 2011 to 2015 and treated with nCCRT via the Taiwan Cancer Registry and related databases. We compared the hazard ratios (HRs) of death using a robust variance estimator. We also evaluated alternative covariables, outcomes, and interval definitions. RESULTS: Our study population included 80 patients for each group; groups were balanced with respect to the observed covariables. There was no significant difference for the HR of death [1.22; 95% confidence interval 0.78-1.91, P = 0.39] when the long interval group was compared to the short interval group. There were also no significant differences when alternative covariables, outcomes, or interval definitions were evaluated. CONCLUSIONS: In this population-based study in modern Asia, we found that for LA-ESqCC patients treated with nCCRT and esophagectomy, overall survival was similar for either long or short intervals between nCCRT and esophagectomy. Randomized controlled trials are needed to verify this finding.

Prolonged persistence of IgM against dengue virus detected by commonly used commercial assays.

BACKGROUND: Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported. METHODS: We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel. RESULTS: Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7-446.9) by SD ELISA, while at 175.7 days (95% CI 121.9-221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively. CONCLUSION: Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year.

High estimated prevalence of asymptomatic dengue viremia in blood donors during a dengue epidemic in southern Taiwan, 2015.

BACKGROUND: Southern Taiwan experienced a severe dengue epidemic in 2015. Adult asymptomatic cases would raise concerns on transfusion-transmitted dengue virus (DENV) infection. The aim of this study was to evaluate the magnitude of such a risk in Tainan City during this epidemic. STUDY DESIGN AND METHODS: The daily prevalence of asymptomatic dengue viremia in blood donors in Tainan City and in selected high-incidence districts during the 2015 dengue epidemic was estimated by an established mathematical model. Duration of viremia, duration of viremia before symptom onset, apparent-to-inapparent infection ratio, and reporting-to-underreporting ratio were four main parameters used in the model. RESULTS: The estimated maximal and mean daily prevalence of asymptomatic dengue viremia in blood donors in Tainan during this dengue epidemic was 74.4 (95% confidence interval [CI], 60.8-88.0) and 15.0 (95% CI, 12.3-17.7) per 10,000, respectively. In the district with the highest incidence, the maximal and mean daily prevalence of asymptomatic viremia was 328.8 (95% CI, 271.1-386.2) and 55.3 (95% CI, 43.4-63.3) per 10,000, respectively. Approximately 234 (95% CI, 191-276) blood components containing DENV were produced during the epidemic. CONCLUSION: Although dengue is currently not endemic in Taiwan, physicians need to be aware of the risk of transfusion-transmitted DENV infection. Our results suggest that screening measures to ensure blood safety should be evaluated and implemented during dengue epidemics even in nonendemic areas. Timely estimation of daily asymptomatic viremia prevalence by districts can help to select high-risk areas for such measures and to evaluate cost-effectiveness.

Risks of anxiety disorders, depressive disorders, and sleep disorders in patients with dengue fever: A nationwide, population-based cohort study.

BACKGROUND: Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied. METHODS: This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS: A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year. CONCLUSION: Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms.

Correction: Dashboard With Bump Charts to Visualize the Changes in the Rankings of Leading Causes of Death According to Two Lists: National Population-Based Time-Series Cross-Sectional Study.

[This corrects the article DOI: 10.2196/42149.].

Discrepancies in dengue burden estimates: a comparative analysis of reported cases and global burden of disease study, 2010-2019.

BACKGROUND: Dengue is a significant mosquito-borne disease. Several studies have utilized estimates from the Global Burden of Disease (GBD) study to assess the global, regional or national burden of dengue over time. However, our recent investigation suggests that GBD's estimates for dengue cases in Taiwan are unrealistically high. The current study extends the scope to compare reported dengue cases with GBD estimates across 30 high-burden countries and territories, aiming to assess the accuracy and interpretability of the GBD's dengue estimates. METHODS: Data for this study were sourced from the GBD 2019 study and various national and international databases documenting reported dengue cases. The analysis targeted the top 30 countries and territories with the highest 10-year average of reported cases from 2010 to 2019. Discrepancies were quantified by computing absolute differences and ratios between the 10-year average of reported cases and GBD estimates. Coefficients of variation (CV) and estimated annual percentage changes (EAPCs) were calculated to assess variations and trends in the two data sources. RESULTS: Significant discrepancies were noted between reported data and GBD estimates in the number of dengue cases, incidence rates, and EAPCs. GBD estimates were substantially higher than reported cases for many entities, with the most notable differences found in China (570.0-fold), India (303.0-fold), Bangladesh (115.4-fold), Taiwan (85.5-fold) and Indonesia (23.2-fold). Furthermore, the GBD's estimates did not accurately reflect the extensive yearly fluctuations in dengue outbreaks, particularly in non-endemic regions such as Taiwan, China and Argentina, as evidenced by high CVs. CONCLUSIONS: This study reveals substantial discrepancies between GBD estimates and reported dengue cases, underscoring the imperative for comprehensive analysis in areas with pronounced disparities. The failure of GBD estimates to represent the considerable annual fluctuations in dengue outbreaks highlights the critical need for improvement in disease burden estimation methodologies for dengue.

Reinvestigation of the risk of stroke after dengue virus infection: A population-based cohort study.

BACKGROUND: Dengue virus (DENV) infection is the most prevalent mosquito-borne viral disease. Stroke is a severe manifestation of dengue. However, few large-scale studies have investigated post-dengue risk of stroke. METHODS: This population-based cohort study included 57,934 newly diagnosed, laboratory-confirmed dengue patients in Taiwan from 2002 to 2015; patients were matched to nondengue individuals by age, sex, and area of residence at a ratio of 1:4 (n = 231,736). We used subdistribution hazard regression to evaluate short-term (≤ 30 days), medium-term (31-365 days), and long-term (1-3 years) risk of stroke after DENV infection. The robustness of the results to unmeasured confounding was assessed with E-values. RESULTS: DENV infection was associated with a significantly increased risk of overall stroke (aSHR 4.51; 95% CI: 3.23-6.32; P < 0.0001; E-value = 8.49), hemorrhagic stroke (aSHR 4.13; 95% CI: 2.20-7.76; P < 0.0001; E-value =7.73), and ischemic stroke (aSHR 3.80; 95% CI: 2.37-6.11; P < 0.0001; E-value = 7.06) within 30 days. Stratified analysis by age showed that the aSHRs for overall stroke, hemorrhagic stroke, and ischemic stroke were larger among dengue patients aged ≥ 65 during the first 30 days. The 30-day risks of overall stroke, hemorrhagic stroke, and ischemic stroke among elderly dengue patients were 6.71, 1.29, and 3.49 per 1000, respectively. No increased risk was observed after 30 days. CONCLUSION: DENV infection was associated with a significant short-term increased risk of stroke. Clinical practitioners should remain alert to patients with stroke-associated symptoms during epidemic seasons, especially elderly patients.

Risks of Acute Cholecystitis, Acute Pancreatitis, and Acute Appendicitis in Patients with Dengue Fever: A Population-Based Cohort Study in Taiwan.

INTRODUCTION: Although cases of acute cholecystitis, acute pancreatitis, and acute appendicitis following dengue virus infections have been documented, very few large-scale studies have investigated the postdengue risk of these acute abdominal conditions. METHODS: This retrospective population-based cohort study included all patients with laboratory-confirmed dengue from 2002 to 2015 in Taiwan and 1:4 nondengue individuals matched by age, sex, area of residence, and symptom onset time. Multivariate Cox proportional hazards regression models were used to investigate the short-term (≤ 30 days), medium-term (31-365 days), and long-term (> 1 year) risks of acute cholecystitis, pancreatitis, and appendicitis after dengue infection, adjusted for age, sex, area of residence, urbanization level, monthly income level, and comorbidities. Bonferroni correction was used for multiple testing; E-values were used to assess the robustness of the results to unmeasured confounding. RESULTS: This study included 65,694 individuals with dengue and 262,776 individuals without dengue. Patients with dengue had a significantly increased risk of acute cholecystitis (adjusted hazard ratio (aHR) 60.21; 95% CI 29.11-124.54; P < 0.0001, E-value = 119.92) and acute pancreatitis (aHR 17.13; 95% CI 7.66-38.29; P < 0.0001, E-value = 33.75) within the first 30 days postinfection compared to those without dengue, but this increased risk was not present after that. The incidence rates of acute cholecystitis and pancreatitis in the first 30 days were 18.79 and 5.27 per 10,000, respectively. No increased risk of acute appendicitis was observed among patients with acute dengue infection. CONCLUSION: This study was the first large epidemiological study to show a significantly increased risk of acute cholecystitis and pancreatitis among patients with dengue during the acute phase of dengue infection, while no such association was observed for acute appendicitis. Early identification of acute cholecystitis and pancreatitis in patients with dengue is crucial for preventing fatal complications.

Re-examination of the risk of dementia after dengue virus infection: A population-based cohort study.

Dengue infection can affect the central nervous system and cause various neurological complications. Previous studies also suggest dengue was associated with a significantly increased long-term risk of dementia. A population-based cohort study was conducted using national health databases in Taiwan and included 37,928 laboratory-confirmed dengue patients aged ≥ 45 years between 2002 and 2015, along with 151,712 matched nondengue individuals. Subdistribution hazard regression models showed a slightly increased risk of Alzheimer's disease, and unspecified dementia, non-vascular dementia, and overall dementia in dengue patients than the nondengue group, adjusted for age, sex, area of residence, urbanization level, income, comorbidities, and all-cause clinical visits within one year before the index date. After considering multiple comparisons using Bonferroni correction, only overall dementia and non-vascular dementia remained statistically significant (adjusted SHR 1.13, 95% CI 1.05-1.21, p = 0.0009; E-value 1.51, 95% CI 1.28-NA). Sensitivity analyses in which dementia cases occurring in the first three or five years after the index dates were excluded revealed no association between dengue and dementia. In conclusion, this study found dengue patients had a slightly increased risk of non-vascular dementia and total dementia than those without dengue. However, the small corresponding E-values and sensitivity analyses suggest the association between dengue and dementia may not be causal.

Re-examination of the risk of autoimmune diseases after dengue virus infection: A population-based cohort study.

Previous studies suggested that dengue was associated with an increased risk of several autoimmune diseases. However, this association still needs to be explored due to the limitations of these studies. A population-based cohort study was conducted using national health databases in Taiwan and included 63,814 newly diagnosed, laboratory-confirmed dengue patients between 2002 and 2015 and 1:4 controls (n = 255,256) matched by age, sex, area of residence and symptom onset time. Multivariate Cox proportional hazard regression models were used to investigate the risk of autoimmune diseases after dengue infection. Dengue patients had a slightly higher risk of overall autoimmune diseases than non-dengue controls (aHR 1.16; P = 0.0002). Stratified analyses by specific autoimmune diseases showed that only autoimmune encephalomyelitis remained statistically significant after Bonferroni correction for multiple testing (aHR 2.72; P < 0.0001). Sixteen (0.025%) dengue patients and no (0%) controls developed autoimmune encephalomyelitis in the first month of follow-up (HR >9999, P < 0.0001), but the risk between groups was not significantly different thereafter. Contrary to previous studies, our findings showed that dengue was associated with an increased short-term risk of a rare complication, autoimmune encephalomyelitis, but not associated with other autoimmune diseases.