Chang Gung Research Database Research Articles

Allergen Tests of Fruit Sensitization Involving Children with Allergic Diseases.

Fruit is a kind of plant food which is rich in nutrients and immune-regulating ingredients. A meta-analysis has demonstrated that fruits have a protective effects against asthma. On the other hand, clinical syndromes of allergic reactions to fruits manifest as an oral allergy syndrome. We aimed to investigate the patterns and associated factors of fruit allergen-specific IgE (sIgE) sensitization among patients with suspected clinical symptoms. Data were extracted from the Chang Gung Research Database. Fruit sensitization in Taiwan was evaluated using the presence of IgE antibodies against specific fruits. The overall prevalence of positive sIgE responses to fruit allergens in Taiwan, in order of decreasing importance, was pineapple, kiwi, banana, and papaya. Children aged 0–18 had a higher positive rate of allergic responses to pineapple, kiwi, banana, and papaya than adults over the age of 18. Positive specific IgE for kiwi, banana, or papaya was more frequent in younger than in older children and children with a higher total IgE of both logarithmic (log) and arithmetic values. The analysis of log IgE for pineapple positive vs. negative children determined an optimal cutoff value, log IgE 2.2, with both sensitivity (0.9) and specificity (0.5). Dermatitis was significantly more prevalent in children with positive IgE for pineapple, kiwi, banana, and papaya than negative specific IgE. The highest positive rate of sIgE against fruits was pineapple among children. Even in older children, the positive rate of pineapple allergens was high. IgE discriminates with and without sIgE for pineapple, with an optimal cutoff of 158.5 U/mL.

Clinical characteristics and outcomes of mixed virus or bacterial infection in children with laboratory-confirmed influenza infection

This study investigated the demographic characteristics and influenza complications of paediatric patients and explored the association of different influenza virus types and viral and bacterial coinfections with disease severity. This retrospective cohort study used data collected in 2010-2016 from the Chang Gung Research Database (CGRD), the largest collection of multi-institutional electronic medical records in Taiwan. Data were retrieved for children aged 0-18 years with laboratory-confirmed influenza. We extracted and analysed the demographic characteristics and the data on clinical features, complications, microbiological information, and advanced therapies of each case. We identified 6193 children with laboratory-confirmed influenza, of whom 1964 (31.7%) were hospitalised. The age of patients with influenza A infection was lower than that of patients with influenza B (4.48 vs. 6.68, p<0.001). Patients with influenza B infection had a higher incidence of myositis or rhabdomyolysis (4.4%, p<0.001) and a higher need for advanced therapies (OR, 1.96; 95% CI, 1.32-2.9, p<0.001). In addition to bacterial (OR, 9.07; 95% CI, 5.29-15.54, p<0.001) and viral coinfection (OR, 7.73; 95% CI, 5.4-11.07, p<0.001), dual influenza A and B infection was also a risk factor for influenza complications (OR, 2.13; 95% CI, 1.47-3.09, p<0.001). Dual influenza A and B infection and bacterial coinfection can contribute to influenza complications. Early recognition of any influenza complication is critical for the timely initiation of organ-specific advanced therapies to improve influenza-associated outcomes.

Risk factors of first and recurrent genitourinary tract infection in patients with type 2 diabetes treated with SGLT2 inhibitors: A retrospective cohort study

AimsThis retrospective study investigated the risk factors of sodium-glucose cotransporter 2 inhibitors (SGLT2i) -related genitourinary tract infection (GUTI). MethodsWe used longitudinal claims data from May 2016 to December 2017 from the Chang Gung Research Database. Diabetic patients who used SGLT2i were included. The baseline characteristics risk factors between patients who had GUTI and no GUTI were analyzed. ResultsThere were 428(3.43%) patients with the first occurrence of urinary tract infection (UTI) and 5(0.04%) patients with genital tract infection (GTI). Female patients aged ≥ 65 years with HbA1c ≥ 9%, eGFR < 60 ml/min/1.73 m2, urine albumin/creatinine ratio (UACR) level ≥30 mg/g, dyslipidemia, diabetic microvascular complications and mood disorder had a higher risk of having the first occurrence of UTI. There was no significant risk factor of GTI. 117 UTI and 3 GTI patients received SGLT2i rechallenging. The recurrent UTI rate was 28.2% and no recurrent GTI was diagnosed. The risk factors included CHD, eGRF < 45 ml/min/1.73 m2, and mood disorder (OR, 95% CI: 4.39, 1.15–16.74; 4.11, 1.51–11.19; 5.93, 1.39–25.34, respectively). ConclusionsIn diabetic patients who had underlying disease of eGRF < 45 ml/min/1.73 m2, CHD, and mood disorder had higher risk of recurrent UTI after rechallenging SGLT2i.

The Pattern of Hemoglobin A1C Trajectories and Risk of Herpes Zoster Infection: A Follow-Up Study.

To investigate the risks of herpes zoster (HZ) infection among heterogeneous HbA1C trajectories of patients with newly diagnosed type 2 diabetes, this cohort study used data from the Chang Gung Research Database (CGRD), from the 10-year period of 1 January 2007 to 31 December 2017. We applied group-based trajectory modeling (GBTM) to identify the patterns of HbA1C trajectories, and multiple Cox proportional hazards regressions were used to estimate the hazard ratio (HR) for the risk of HZ infection with adjustment of age, sex, and comorbidities. This study enrolled 121,999 subjects to perform the analysis. The GBTM identified four HbA1C trajectories: ‘good control’ (58.4%), ‘high decreasing’ (8.9%), ‘moderate control’ (25.1%), and ‘poor control’ (7.6%) with the mean HbA1C of 6.7% (50 mmol/mol), 7.9% (63 mmol/mol), 8.4% (68 mmol/mol), and 10.7% (93 mmol/mol) respectively. The risk of HZ was significantly higher in the poor control with an HR = 1.44 (95% CI 1.26–1.64) after adjustment for confounders and comorbidities. The risk of HZ infection for the high decreasing group (initially poor then rapidly reaching optimal control) was nonsignificant compared to the good control group. In conclusion, the patients with poor glycemic control (mean HbA1C = 10.7%) had the highest risk of HZ infection. The patients with initial hyperglycemia then reaching optimal control could have a lower risk of HZ infection.

Effects of dexmedetomidine on surgery for type A acute aortic dissection outcome

No study has evaluated the effect of dexmedetomidine in patients who received surgery for type A aortic dissection. This is the first study to evaluate the effect of dexmedetomidine in aortic dissection patients. This study was executed using data from the Chang Gung Research Database in Taiwan. The CGRD contains the multi‐institutional standardized electronic medical records from seven Chang Gung Memorial hospitals, the largest medical system in Taiwan. We retrospectively evaluate patients who received surgery for acute type A aortic dissection between January 2014 and December 2018. Overall, 511 patients were included, of whom 104 has received dexmedetomidine infusion in the postoperative period. One-to-two propensity score-matching yielded 86 cases in the dexmedetomidine group and 158 cases in the non-dexmedetomidine group. The in-hospital mortality and composite outcome including all-cause mortality, acute kidney injury, delirium, postoperative atrial fibrillation, and respiratory failure, were considered primary outcomes. The in-hospital mortality and composite outcome were similar between groups. The risk of Acute Kidney Injury Network stage 3 acute kidney injury was significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (8.1% vs 19.0%; OR, 0.38; 95% CI, 0.17–0.86; p = 0.020. The risk of newly-onset dialysis was also significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (4.7% vs 13.3%; OR, 0.32; 95% CI, 0.11–0.90; p = 0.031). Post-operative dexmedetomidine infusion significantly reduced the rate of severe acute kidney injury and newly-onset dialysis in patients who received surgery for acute type A aortic dissection.

Analysis of Anticoagulation Therapy and Anticoagulation-Related Outcomes Among Asian Patients After Mechanical Valve Replacement

Current international normalized ratio (INR) guidelines are based on trials involving European and US populations. To our knowledge, no adequate study involving Asian patients has been conducted to date. To evaluate the association between INR and anticoagulation-related outcomes in an Asian population after mechanical aortic valve replacement (AVR) or mitral VR (MVR). This retrospective cohort study was conducted between 2001 and 2018, with follow-up until December 31, 2018, among patients who underwent AVR, MVR, or combined AVR-MVR at 3 medical centers and 4 regional hospitals and contributed electronic medical records to the Chang Gung Research Database. Exclusion criteria were missing demographic characteristics, younger than 20 years, fewer than 2 INR records, and having died during the hospitalization of the index surgery. Bleeding and thromboembolic complications were analyzed. The possibility of nonlinearity and cutoff potential for the INR were explored using a logistic regression model, which considered the INR a restricted cubic spline (RCS) variable. The study population consisted of 900 patients, with 525 (58.3%) men and 375 (41.7%) women and a mean (SD) age of 52.0 (12.5) years. Overall, 474 (52.7%) received AVR alone, 329 (36.6%) received MVR alone, and 97 (10.8%) received combined AVR-MVR. All patients had at least 2 INR examinations after discharge, providing 16 676 INR records for the AVR group and 18 207 for the MVR and combined AVR-MVR groups. In the AVR group, the RCS model showed that higher risks of composite thromboembolic events were associated with an INR of less than 2.0 or greater than 2.6 vs an INR of 2.0, and a higher risk of bleeding events was associated with an INR of less than 1.8 or greater than 2.4 vs an INR of 2.0. When treating the INR as a categorical variable, the risk of composite thromboembolic and composite bleeding events was significantly higher among patients with INRs less than 1.5 (adjusted odds ratio [aOR], 2.55; 95% CI, 1.37-4.73) and with INRs of 3.0 or greater (aOR, 3.48; 95% CI, 1.95-6.23) vs those with INRs between 2.0 and 2.5.In the MVR and combined AVR-MVR groups, higher risks of composite thromboembolic events were associated with an INR of less than 2.1 or greater than 2.7 vs an INR of 2.5, and a higher risk of bleeding events was associated with an INR of less than 2.1 or greater than 2.8 vs an INR of 2.5. When treating the INR as a categorical variable, the risk of a composite bleeding events was significantly higher among patients with INRs of 3.5 or greater (aOR, 2.25; 95% CI, 1.35-3.76) vs those with INRs between 2.5 and 3.0. Among Asian patients in this study, the incidence of thromboembolic events in the MVR group with INRs in the range of 2.0 to 2.5 was not significantly higher than that among those with INRs in the range of 2.5 to 3.0; in the AVR group, the incidence for those with INRs in 1.5 to 2.0 range was not significantly higher than for those with INRs in the range of 2.0 to 2.5.

Direct Oral Anticoagulants Are Associated with Superior Survival Outcomes than Warfarin in Patients with Head and Neck Cancers.

Simple SummaryPatients with head and neck cancers may suffer from cancer-associated thromboembolism and direct oral anticoagulants (DOACs) are a potential new therapeutic option. We aimed to determine the clinical impact of DOACs compared with traditional anticoagulants on the survival of patients with head and neck cancers. In our study, DOAC users had significantly better disease-specific survival (DSS) and higher overall survival (OS) rates than warfarin users and those who did not use any anticoagulant. Further, there were no significant differences in the occurrence rate of bleeding or ischemic events between DOAC and warfarin users. Our study suggested that DOACs can be a treatment choice or prophylaxis for tumor emboli in head and neck cancer patients and that they might be a better choice than traditional anticoagulants.Increasing clinical evidence supports the use of direct oral anticoagulants (DOACs) as a potential new therapeutic option for patients suffering from cancer-associated thromboembolism. However, the clinical impact of DOACs compared with traditional anticoagulants on the survival of patients with head and neck cancer has not been well studied. A total of 1025 patients diagnosed as having head and neck cancer, including 92 DOAC users, 113 warfarin users, and 820 nonusers of anticoagulants, were selected from the Chang Gung Research Database between January 2001 and December 2019. The patients were matched using the propensity-score method. The survival rates were estimated among the three groups using the Kaplan–Meier method. The protective effects and side effects of the two anticoagulants were compared using the chi-square test. The death rate (18 patients, 19.57%) in patients using DOACs was significantly lower than that in patients using warfarin (68 patients, 60.18%) and those not using any anticoagulant (403 patients, 49.15%). DOAC users had significantly better disease-specific survival (DSS) than warfarin users (p = 0.019) and those who did not use any anticoagulant (p = 0.03). Further, DOAC users had significantly higher overall survival (OS) rates than warfarin users and those who did not use any anticoagulant (p = 0.003). Patients with oropharyngeal and laryngeal cancer and DOAC users had a significantly lower hazard ratio for survival, whereas patients with American Joint Committee on Cancer stage IV disease and those receiving multidisciplinary treatment (e.g., surgery with radiotherapy or concurrent radiochemotherapy) had a significantly higher hazard ratio for survival. Among them, patients with laryngeal cancer (HR = 0.47, 95% CI = 0.26–0.86, p = 0.0134) and DOAC users (HR = 0.53, 95% CI = 0.29–0.98, p = 0.042) had the lowest hazard ratio from DSS analysis. Similarly, patients with laryngeal cancer (HR = 0.48, 95% CI = 0.30–0.76, p = 0.0018) and DOAC users (HR = 0.58, 95% CI = 0.36–0.93, p = 0.0251) had the lowest hazard ratio from OS analysis. As for the protective effects or side effects of anticoagulants, there were no significant differences in the occurrence rate of bleeding or ischemic events between DOAC and warfarin users. In our study, DOACs were found to be better than warfarin in terms of survival in patients with head and neck cancer. As regards thromboembolism prevention and side effects, DOACs were comparable to warfarin in our patients. DOACs can be a treatment choice or prophylaxis for tumor emboli in head and neck cancer patients and they might be a better choice than traditional anticoagulants according to the results of our study.

Number of Kawasaki Disease Admissions Is Associated with Number of Domestic COVID-19 and Severe Enterovirus Case Numbers in Taiwan.

Background: Non-pharmaceutical interventions (NPIs) introduced in response to the COVID-19 pandemic, including mask-wearing and social distancing, have changed the prevalence of circulating viruses in the community. Since viral infections represent a potential triggering factor for the development of Kawasaki disease (KD), we examined the relationship between KD admission rates and the number of COVID-19, severe influenza, and severe enterovirus infections both before and after the COVID-19 pandemic. Methods: We conducted a retrospective study using data obtained from the Chang Gung Research Database (including seven Taiwanese hospitals and more than 10,000 beds) and the Centers for Disease Control in Taiwan from January 2018 to December 2020. We recorded the number of KD admissions, as well as COVID-19, severe influenza, and severe enterovirus infections. Results: The numbers of KD admissions, severe enterovirus infections, and severe influenza infections were significantly lower from April to September 2020. The number of KD hospitalizations was positively correlated with the number of domestic COVID-19 cases (p = 0.001). A decrease in KD admission numbers was positively correlated with a decrease in severe enterovirus case numbers (p = 0.007). Conclusion: Our findings provide further evidence that viral infections may be an important trigger factor in the development of KD. Therefore, NPIs may not only prevent transmissible viral infections in children, but also decrease the risk of KD.

Influence of Comorbidities and Airway Clearance on Mortality and Outcomes of Patients With Severe Bronchiectasis Exacerbations in Taiwan.

Bronchiectasis is characterized by systemic inflammation and multiple comorbidities. This study aimed to investigate the clinical outcomes based on the bronchiectasis etiology comorbidity index (BACI) score in patients hospitalized for severe bronchiectasis exacerbations. We included non-cystic fibrosis patients hospitalized for severe bronchiectasis exacerbations between January 2008 and December 2016 from the Chang Gung Research Database (CGRD) cohort. The main outcome was the 1-year mortality rate after severe exacerbations. We used the Cox regression model to assess the risk factors of 1-year mortality. Of 1,235 patients who were hospitalized for severe bronchiectasis exacerbations, 641 were in the BACI < 6 group and 594 in the BACI ≥ 6 group. The BACI ≥ 6 group had more previous exacerbations and a lower FEV1. Pseudomonas aeruginosa (19.1%) was the most common bacterium, followed by Klebsiella pneumoniae (7.5%). Overall, 11.8% of patients had respiratory failure and the hospital mortality was 3.0%. After discharge, compared to the BACI < 6 group, the BACI ≥ 6 group had a significantly higher cumulative incidence of respiratory failure and mortality in a 1-year follow-up. The risk factors for 1-year mortality in a multivariate analysis include age [hazard ratio (HR) 4.38, p = 0.01], being male (HR 4.38, p = 0.01), and systemic corticosteroid usage (HR 6.35, p = 0.001), while airway clearance therapy (ACT) (HR 0.50, p = 0.010) was associated with a lower mortality risk. An increased risk of respiratory failure and mortality in a 1-year follow-up after severe exacerbations was observed in bronchiectasis patients with multimorbidities, particularly older age patients, male patients, and patients with a history of systemic corticosteroid use. ACT could effectively improve the risk for 1-year mortality.

The Risk Factors of Severe Hypoglycemia in Older Patients with Dementia and Type 2 Diabetes Mellitus.

Background: The adequate glycemic control and risk factors for hypoglycemia in older patients with dementia and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to analyze the status of glycemic control and determine the risk of hypoglycemia among these groups. Methods: A hospital admission record due to hypoglycemia through an emergency room with glucose supplementation in the Chang Gung Memorial Hospital was identified as a hypoglycemic event. Patients with dementia and T2DM without hypoglycemic events throughout the study period were defined as the control group. We gathered patients aged ≥65 years with a diagnosis of Alzheimer’s dementia (AD) and T2DM between 2001 and 2018 in the Chang Gung Research Database (CGRD). We extracted data included medication use, diagnoses, and biochemistry data from hospital records. Results: A total of 3877 older patients with dementia and T2DM with regular visits to the outpatient department were enrolled in this study. During the two-year follow-up period, 494 participants (12.7%) experienced hypoglycemia. Multivariable logistic multivariable regression models for hypoglycemic events showed that metformin had a protective effect (odds ratio (OR) = 0.75, p = 0.023), insulin had the highest risk (OR = 4.64, p < 0.001). Hemoglobin A1c (HbA1c) levels were not correlated with hypoglycemic events (OR = 0.95, p = 0.140). Patients with hypoglycemic episodes had a significantly higher proportion of ≥2 Charlson Comorbidity Index scores than those without hypoglycemic episodes (83.2% versus 56.4%, p < 0.001). Conclusions: Drug regimen affects hypoglycemic episodes but not HbA1c in older patients with dementia and T2DM. In addition, patients with more comorbidities experience an increased risk of hypoglycemia.

Increased Incident Alzheimer's Disease among Individuals with Varicose Veins: A Population-Based Cohort Study.

Varicose vein may be related to increased risk of comorbidities and decreased cognitive function in the elderly, but little is known about the association between varicose vein and Alzheimer's disease. To evaluate whether there is an association between varicose veins and Alzheimer's disease. The study subjects of this cohort study were selected based on Chang Gung Research Database from January 1, 2003, to December 31, 2012. Follow-up ended December 31, 2017. A population-based study Participants: Patients aged 45 years and older with varicose veins were enrolled, and the participants of control group were selected by matching with gender, age, and index date at a 4:1 ratio. The hazard ratios associated with varicose veins were estimated using Cox regression analysis with competitive risk model. Incidence rates of Alzheimer's disease, was assessed in people with and without varicose veins. A total of 9,601 patients with varicose veins and 38,404 matched controls were enrolled in the study. The varicose veins group had higher incidence rates than the control group for Alzheimer's disease (12.60 vs 6.24 per 10,000 person-years; Hazard ratio, 1.647 [95% confidence interval, 1.326- 2.045, p<0.001]). Patients with complicated varicose veins had increased incidence of Alzheimer's disease than uncomplicated cases (adjusted HR, 1.474; 95% CI, 1.034-2.101, P=0.032). The present study demonstrated a positive association between the varicose veins and Alzheimer's disease. Physicians should be alerted to cognitive function in patients with varicose veins, especially those with presence of inflammation and ulcerations.

A Machine Learning Model for Predicting Unscheduled 72 h Return Visits to the Emergency Department by Patients with Abdominal Pain.

Seventy-two-hour unscheduled return visits (URVs) by emergency department patients are a key clinical index for evaluating the quality of care in emergency departments (EDs). This study aimed to develop a machine learning model to predict 72 h URVs for ED patients with abdominal pain. Electronic health records data were collected from the Chang Gung Research Database (CGRD) for 25,151 ED visits by patients with abdominal pain and a total of 617 features were used for analysis. We used supervised machine learning models, namely logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGB), and voting classifier (VC), to predict URVs. The VC model achieved more favorable overall performance than other models (AUROC: 0.74; 95% confidence interval (CI), 0.69–0.76; sensitivity, 0.39; specificity, 0.89; F1 score, 0.25). The reduced VC model achieved comparable performance (AUROC: 0.72; 95% CI, 0.69–0.74) to the full models using all clinical features. The VC model exhibited the most favorable performance in predicting 72 h URVs for patients with abdominal pain, both for all-features and reduced-features models. Application of the VC model in the clinical setting after validation may help physicians to make accurate decisions and decrease URVs.

Discharge status validation of the Chang Gung Research database in Taiwan

BackgroundThe Chang Gung Research Database (CGRD) is the largest multi-institutional electronic medical records database in Taiwan and has been widely used to establish evidence studies. However, the accuracy of CGRD has rarely been validated. This study aims to validate the discharge status, especially with a focus on mortality, of admission data under CGRD. MethodsWe constructed an observational study using CGRD linked with TDR to validate the discharge status. The CGRD and TDR data were obtained from the Chang Gung Memorial Hospital system and the Health and Welfare Data Science Center, respectively. The accuracy, positive predictive value (PPV), and underestimated mortality rate (UEM) were employed as indicators for validation. Year, sex, age, and the primary cause for admission (PCA) were analyzed. ResultsA total of 1,972,044 admission records under CGRD were analyzed. The overall accuracy for mortality coding on discharge status was higher than 97% within one week after discharge. The accuracy increased by year and was more than 98% after 2010. A similar result was observed in UEM; the UEM within one week was lower than 10% after 2010. These indicators varied by age group and PCA—elderly patients had relatively lower accuracy and higher UEM (approximately 11%). The presence of UEM within one week was better but varied by disease. ConclusionsConsidering the data accuracy and UEM discharge status, prioritizing the use of inpatient data after 2010 under CGRD for mortality outcome follow-up studies is recommended.

Risk of incident cataract in patients with psoriasis: A population-based cohort study.

Patients with psoriasis are predisposed to ocular complications. However, there is a paucity of data addressing the association between psoriasis and subsequent cataract development. The present study was conducted to evaluate whether there is an increased risk of cataract among patients with psoriasis. The study subjects of this cohort study were selected based on Chang Gung Research Database from 1 January 2003 to 31 December 2012. Follow-up ended 31 December 2017. Patients aged 20years and older with psoriasis were enrolled. The participants of the control group were selected by matching with sex, age, and index date at a 4:1 ratio. Patients previously diagnosed with cataract were excluded. The hazard ratios associated with psoriasis were estimated using Cox regression analysis with competitive risk model. We also evaluated the relationship between the risk of cataract and systemic therapies as well as phototherapy and topical corticosteroid in patients with psoriasis. A total of 6823 patients with psoriasis and 27292 matched controls were enrolled in the study. The psoriasis group had higher incidence rates than the control group for cataract (44.08 vs 19.45 per 10000 person-years; adjusted hazard ratio, 1.778 [95% confidence interval, 1.530-2.066; p<0.001]). Psoriatic patients receiving phototherapy for more than 200 sessions had a higher risk of cataract (adjusted hazard ratio, 2.933; 95% confidence interval, 1.192-7.218; p=0.019), especially those receiving narrowband ultraviolet B therapy. The present study demonstrated a positive association between psoriasis and cataract. Physicians should be alert to visual function in patients with psoriasis, especially those receiving long-term phototherapy.

Angiotensin II receptor blockers and oral squamous cell carcinoma survival: A propensity-score-matched cohort study.

Angiotensin II receptor blockers (ARBs) improve the survival rates of patients with various cancers. However, it remains unclear whether ARBs confer a survival benefit on patients with oral squamous cell carcinoma (OSCC). Here, we assessed the associations between ARB use and survival in patients with OSCC of different stages. This was a 10-year retrospective cohort study of OSCC patients. We enrolled 7,558 patients diagnosed with oral cancer between January 2007 and December 2017 whose details had been entered into the Chang Gung Research Database. Seven hundred and fourteen patients were recruited from the Chang Gung Research Database after performing 1:1 propensity score-matching between ARB users and non-users. Cox's regression models with adjusted covariates were employed to detect factors influencing the survival rates of patients with OSCC. Kaplan-Meier analysis revealed that the overall survival (OS) rate of 180-day ARB users increased (p = 0.038). Cox's regression models indicated that ARB use, younger patients, early-stage OSCC, and patients without diabetes mellitus were independently prognostic of improved OS. Increased OS was more prominent in 180-day ARB users in stage III, Iva, and IVb categories. ARB use for more than 180 days is associated with an increased survival rate and is a positive, independent prognostic factor in patients with OSCC. A further two-arm study should be conducted to confirm the clinical usefulness of ARBs in OSCC patients.

The impact on renal function after long-term use of anticoagulants in atrial fibrillation patients

ObjectiveLong-term oral anticoagulant should be considered or recommended in patients with atrial fibrillation (AF) and CHA2DS2VASc score ≥ 1 for stroke prevention. Warfarin and different direct oral anticoagulants (DOACs) are metabolized differently by the kidney. The impact on renal function after long-term use of anticoagulants in the patients with AF remains unclear. This study aimed to compare DOACs and warfarin’s impact on the decline in renal function from a large cohort with AF.MethodsThis study included patients with nonvalvular AF from 2000 to 2018, mainly through the medical history (ICD code) of the Chang Gung Research Database. Baseline estimated glomerular filtration rate (eGFR), follow-up eGFR and the change in eGFR between 2-year eGFR and baseline eGFR were compared between different DOACs and warfarin after propensity score matching. The primary study endpoint was acute kidney injury (AKI).Results3657 patients were enrolled in this study and the mean observation time was 3.3 ± 0.9 years. During the observation period, there was a significantly higher incidence of AKI during follow-up in the warfarin group than in the different DOAC groups before and after propensity score matching (before: warfarin vs. DOAC: 9.2% vs. 5.2%, p < 0.001; after: warfarin vs. DOAC: 8.9% vs. 4.4%, p < 0.001). There was no difference in the incidence of AKI between dabigatran group and anti-factor Xa inhibitor group after propensity score matching. The incidence of AKI was similar among rivaroxaban, apixaban and edoxaban groups after propensity score matching. The change in eGFR between 2-year eGFR and baseline eGFR did not differ between the warfarin and DOAC groups after propensity score matching (warfarin vs. DOAC: − 1.27 ± 20.32 vs. -1.94 ± 17.24 mL/min/1.73 m2, p = 0.461).ConclusionsDuring the mean observation time of 3.3 ± 0.9 years, warfarin was associated with a higher incidence of AKI compared with DOACs. The decline in renal function did not differ among warfarin and different DOAC groups.

Initial in-hospital heart rate is associated with long-term survival in patients with acute ischemic stroke

AimsIncreased heart rate has been associated with stroke risk and outcomes. The purpose of this study was to explore the long-term prognostic value of initial in-hospital heart rate in patients with acute ischemic stroke (AIS).MethodsWe analyzed data from 21,655 patients with AIS enrolled (January 2010–September 2018) in the Chang Gung Research Database. Mean initial in-hospital heart rates were averaged and categorized into 10-beat-per-minute (bpm) increments. The primary and secondary outcomes were all-cause mortality and cardiovascular death. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable adjusted Cox proportional hazard models, using the heart rate < 60 bpm subgroup as the reference.ResultsThe adjusted HRs for all-cause mortality were 1.23 (95% CI 1.08–1.41) for heart rate 60–69 bpm, 1.74 (95% CI 1.53–1.97) for heart rate 70–79 bpm, 2.16 (95% CI 1.89–2.46) for heart rate 80–89 bpm, and 2.83 (95% CI 2.46–3.25) for heart rate ≥ 90 bpm compared with the reference group. Likewise, heart rate ≥ 60 bpm was also associated with an increased risk of cardiovascular death (adjusted HR 1.18 [95% CI 0.95–1.46] for heart rate 60–69 bpm, 1.57 [95% CI 1.28–1.93] for heart rate 70–79 bpm, 1.98 [95% CI 1.60–2.45] for heart rate 80–89 bpm, and 2.36 [95% CI 1.89–2.95] for heart rate ≥ 90 bpm).ConclusionsHigh initial in-hospital heart rate is an independent predictor of all-cause mortality and cardiovascular death in patients with AIS.Graphical abstract

Risk of Enteric Infection in Patients with Gastric Acid Supressive Drugs: A Population-Based Case-Control Study.

: BackgroundLong-term use of gastric-acid-suppressive drugs is known to be associated with several adverse effects. However, the association between enteric infection and acid suppression therapy is still uncertain. This study aimed to evaluate the association between gastric acid suppression and the risk of enteric infection. Materials and Methods: We conducted a population-based case-control study using the data from Chang Gung Research Database (CGRD) in Taiwan. Between January 2008 and December 2017, a total of 154,590 adult inpatients (age > 18) were identified. A pool of potential eligible controls according to four propensity scores matching by sex, age, and index year were extracted (n = 89,925). Subjects with missing data or who received less than 7 days of proton pump inhibitors (PPIs) and/or H2-receptor antagonists (H2RAs) were excluded. Finally, 17,186 cases and 69,708 corresponding controls were selected for analysis. The use of PPIs and H2RAs, the result of microbiological samples, and co-morbidity conditions have been analyzed. Confounders were controlled by conditional logistic regression. Results: 32.84% of patients in the case group used PPIs, compared with 7.48% in the control group. Of patients in the case group, 9.9% used H2RAs, compared with 6.9% in the control group. Of patients in the case group, 8.3% used a combination of PPIs and H2RAs, compared with 2.7% in the control group. The most common etiological pathogens were Enterococcus (44.8%), Clostridioides difficile (34.5%), and Salmonella spp. (10.2%). The adjusted odds ratio (OR) for PPI use with enteric infection was 5.526 (95% confidence interval [CI], 5.274–5.791). For H2RAs, the adjusted odds ratio was 1.339 (95% confidence interval [CI], 1.261–1.424). Compared to the control group, persons with enteric infection had more frequent acid-suppressive agent usage. Conclusions: This study demonstrates that gastric-acid-suppressive drug use is associated with an increased risk of enteric infection after adjusting for potential biases and confounders.

Clinical outcomes of Sacubitril/Valsartan in patients with acute heart failure: A multi-institution study.

BackgroundThe effectiveness and safety of initiating sacubitril/valsartan therapy among patients who are hospitalized for acute heart failure (HF) is unclear.MethodsA cohort of 3736 patients with HF with reduced ejection fraction (HFrEF) hospitalized for acute HF was identified from Chang Gung Research Database between January 1, 2016 and August 31, 2019. The risks of rehospitalization for HF and death associated with sacubitril/valsartan therapy compared to angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy were evaluated. We used stabilized inverse probability of treatment weighting to balance the baseline covariates. The risks of fatal and non-fatal outcomes between the groups were compared using a Cox proportional hazard model and Fine and Gray subdistribution hazard model, respectively.FindingsThe composite of rehospitalization for HF and death occurred in 22.9% of the patients in the sacubitril/valsartan group compared to 32.6% in the ACEI/ARB group (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52–0.97) after a mean follow-up period of 11.8 months. The sacubitril/valsartan group had a lower risk of rehospitalization for HF (subdistribution HR 0.83, 95% CI 0.74–0.92) and all-cause death (HR 0.51, 95% CI 0.27–0.94). There were no significant differences in the rates of worsening renal function or severe hyperkalemia between the two groups.InterpretationIn real-world practice, initiating sacubitril/valsartan therapy among patients with HFrEF who were hospitalized for acute HF was associated with a lower rate of rehospitalization for HF and death compared with ACEI/ARB therapy.FundingThis study was supported by Novartis Pharmaceuticals.

Neutrophil-to-lymphocyte ratio is a marker for acute kidney injury progression and mortality in critically ill populations: a population-based, multi-institutional study.

BackgroundsNeutrophil-to-lymphocyte ratio (NLR), a surrogate marker of systemic response to physiological stress, is used for prognosis prediction in many diseases. However, the usefulness of this marker for predicting acute kidney injury (AKI) progression is unclear.MethodsThis retrospective study was based on the Chang Gung Research Database. Patients admitted to the intensive care unit with a diagnosis of stage 1 or 2 AKI were identified. The primary outcome was a composite of progression to stage 3 AKI, requirement of renal replacement therapy, or 14-day in-hospital mortality. The association between NLR and the primary outcome was examined using a logistic regression model and multivariable analysis. The nonlinearity and cutoff points of this relationship were determined using a restricted cubic spline model.ResultsA total of 10,441 patients were enrolled. NLR level at the time of stage 1–2 AKI diagnosis was a marker of adverse outcomes. After adjustment for confounders, NLR was independently associated with the composite outcome of AKI progression, renal replacement therapy, or mortality. The restricted cubic spline model revealed a J-shaped curve, with the lowest odds ratio for an NLR between 7 and 38. Subgroup analysis revealed linear and J-shaped relationships between NLR and the primary outcome in patients admitted to the intensive care unit for medical reasons and for cardiovascular surgery, respectively.ConclusionsNLR is an independent marker of AKI progression and in-hospital mortality. Because it is readily available in daily practice, it might be used for risk stratification in the AKI population.Graphic abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40620-021-01162-3.