Increased risk of chronic fatigue syndrome following infection: a 17-year population-based cohort study.

BACKGROUND: Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from common pathogens, including typical bacteria, and the subsequent risk of developing CFS. The analysis is based on data from Taiwan's National Health Insurance Research Database. METHODS: From 2000 to 2017, we included a total of 395,811 cases aged 20 years or older newly diagnosed with infection. The cases were matched 1:1 with controls using a propensity score and were followed up until diagnoses of CFS were made. RESULTS: The Cox proportional hazards regression analysis was used to estimate the relationship between infection and the subsequent risk of CFS. The incidence density rates among non-infection and infection population were 3.67 and 5.40 per 1000 person-years, respectively (adjusted hazard ratio [HR] = 1.5, with a 95% confidence interval [CI] 1.47-1.54). Patients infected with Varicella-zoster virus, Mycobacterium tuberculosis, Escherichia coli, Candida, Salmonella, Staphylococcus aureus and influenza virus had a significantly higher risk of CFS than those without these pathogens (p < 0.05). Patients taking doxycycline, azithromycin, moxifloxacin, levofloxacin, or ciprofloxacin had a significantly lower risk of CFS than patients in the corresponding control group (p < 0.05). CONCLUSION: Our population-based retrospective cohort study found that infection with common pathogens, including bacteria, viruses, is associated with an increased risk of developing CFS.

Assessment of factors influencing physicians' intention to prescribe transfusion using the theory of planned behavior.

BACKGROUND: Blood shortage is a persistent problem affecting Taiwan's health-care system. The theory of planned behavior (TPB) has been commonly used in studies of health advocacy. The purpose of this study was to develop a questionnaire measuring clinicians' intention to prescribe transfusion based on the TPB. METHOD: A questionnaire comprising 15 items for assessing clinicians' intention to prescribe blood transfusion was developed, and it collected demographic characteristics, tested patient blood management (PBM) and perceived knowledge of PBM. Furthermore, the questionnaire contained four subscales related to the TPB. A total of 129 clinicians participated in this pilot study between July and December2020. Item analysis and exploratory factor analysis were conducted to examine the validity and reliability of this measurement instrument. RESULTS: The results indicated no statistically significant correlations between the demographic characteristics and PBM test scores. Regarding perceived knowledge, the results of a one-way analysis of variance revealed that the effect of age, hierarchy of doctors, and education level were significant. In terms of subjective norms, a significant effect on education level was noted [t (129) = 2.28, p < 0.05], with graduate school graduates receiving higher scores than college graduates. An analysis of variance demonstrated the effects of hierarchy, education level, and medical specialty on perceived behavioral control. The results of the regression analyses revealed that perceived knowledge (ß = 0.32, p < 0.01) and subjective norms (ß = 0.22, p < 0.05) were significantly related to clinicians' behavioral intentions. CONCLUSIONS: This study revealed that factors affecting clinicians' blood transfusion management can be explained using the TPB-based questionnaire. This study demonstrated that physicians' perceptions of whether most people approve of PBM and their self-assessment of their PBM knowledge affect their intentions to proceed with PBM. According to this finding, a support system among physicians must be established and maintained to increase physicians' confidence in promoting PBM.

Penalized Model-Based Unsupervised Phenomapping Unravels Distinctive HFrEF Phenotypes With Improved Outcomes Discrimination From Sacubitril/Valsartan Treatment Independent of MAGGIC Score.

Background The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P<0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. Conclusions Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.

Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan.

OBJECTIVE: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. METHODS: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. RESULTS: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. CONCLUSION: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

The trends in the incidence and thrombosis-related comorbidities of antiphospholipid syndrome: a 14-year nationwide population-based study.

BACKGROUND: This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database. METHODS: Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000-2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed. RESULTS: The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000-2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren's syndrome, and polymyositis. CONCLUSIONS: Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS.

Treatments of chronic fatigue syndrome and its debilitating comorbidities: a 12-year population-based study.

BACKGROUND: This study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health Insurance Research Database. METHODS: 6306 patients identified as having CFS during the 2000-2012 period and 6306 controls (with similar distributions of age and sex) were analyzed. RESULT: The patients with CFS were predominantly female and aged 35-64 years in Taiwan and presented a higher proportion of depression, anxiety disorder, insomnia, Crohn's disease, ulcerative colitis, renal disease, type 2 diabetes, gout, dyslipidemia, rheumatoid arthritis, Sjogren syndrome, and herpes zoster. The use of selective serotonin receptor inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), Serotonin antagonist and reuptake inhibitors (SARIs), Tricyclic antidepressants (TCAs), benzodiazepine (BZD), Norepinephrine-dopamine reuptake inhibitors (NDRIs), muscle relaxants, analgesic drugs, psychotherapies, and exercise therapies was prescribed significantly more frequently in the CFS cohort than in the control group. CONCLUSION: This large national study shared the mainstream therapies of CFS in Taiwan, we noticed these treatments reported effective to relieve symptoms in previous studies. Furthermore, our findings indicate that clinicians should have a heightened awareness of the comorbidities of CFS, especially in psychiatric problems.

Association of Female Menopause With Atrioventricular Mechanics and Outcomes.

Background: Despite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes. Objective: To study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes. Methods: Among 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking. Results: Post-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e', lower LV GLS (0.37, 95%CI 0.04-0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01-0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00-1.07], impaired GLS (aHR 0.87, 95%CI 0.78-0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90-0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69-64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01-3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79-18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well. Conclusion: Menopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further.

Building a model for predicting metabolic syndrome using artificial intelligence based on an investigation of whole-genome sequencing.

BACKGROUND: The circadian system is responsible for regulating various physiological activities and behaviors and has been gaining recognition. The circadian rhythm is adjusted in a 24-h cycle and has transcriptional-translational feedback loops. When the circadian rhythm is interrupted, affecting the expression of circadian genes, the phenotypes of diseases could amplify. For example, the importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed as mutations in genes coding for core components of the clock result in diseases. This study will investigate the association between circadian genes and metabolic syndromes in a Taiwanese population. METHODS: We performed analysis using whole-genome sequencing, read vcf files and set target circadian genes to determine if there were variants on target genes. In this study, we have investigated genetic contribution of circadian-related diseases using population-based next generation whole genome sequencing. We also used significant SNPs to create a metabolic syndrome prediction model. Logistic regression, random forest, adaboost, and neural network were used to predict metabolic syndrome. In addition, we used random forest model variables importance matrix to select 40 more significant SNPs, which were subsequently incorporated to create new prediction models and to compare with previous models. The data was then utilized for training set and testing set using five-fold cross validation. Each model was evaluated with the following criteria: area under the receiver operating characteristics curve (AUC), precision, F1 score, and average precision (the area under the precision recall curve). RESULTS: After searching significant variants, we used Chi-Square tests to find some variants. We found 186 significant SNPs, and four predicting models which used 186 SNPs (logistic regression, random forest, adaboost and neural network), AUC were 0.68, 0.8, 0.82, 0.81 respectively. The F1 scores were 0.412, 0.078, 0.295, 0.552, respectively. The other three models which used the 40 SNPs (logistic regression, adaboost and neural network), AUC were 0.82, 0.81, 0.81 respectively. The F1 scores were 0.584, 0.395, 0.574, respectively. CONCLUSIONS: Circadian gene defect may also contribute to metabolic syndrome. Our study found several related genes and building a simple model to predict metabolic syndrome.

How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study.

BACKGROUND: Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan. METHODS: 7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000-2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011. RESULTS: The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person-years among the non-Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03-1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02-1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86-3.38). CONCLUSIONS: The data from this population-based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.

Variant Aldehyde Dehydrogenase 2 (ALDH2*2) as a Risk Factor for Mechanical LA Substrate Formation and Atrial Fibrillation with Modest Alcohol Consumption in Ethnic Asians.

Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06-2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

The Risk of Developing Osteoporosis in Hemolytic Anemia-What Aggravates the Bone Loss?

Hemolytic anemia (HA) renders erythropoietic stress on the bone marrow and has been linked to osteoporosis. In this nationwide retrospective cohort study, we examined this correlation by utilizing the Taiwan National Health Insurance Research Database (NHIRD). We identified two cohorts, matching population with and without HA in a 1:4 ratio. A total of 2242 HA patients and 8968 non-HA patients were enrolled. Patients with HA had a significantly higher cumulative incidence (log-rank test p = 0.0073), higher incidence density (5.11 vs. 3.76 per 1000 persons-years), and a 1.31-fold risk of developing osteoporosis than non-HA patients (aHR = 1.31, 95% C.I. 1.04-1.63, p = 0.01). After adjusting for age, sex, and comorbidities, patients with factors including female (aHR = 2.57, 95% C.I. 2.05-3.22, p < 0.001), age > 65 (aHR = 9.25, 95% C.I. 7.46-11.50, p < 0.001), diagnosis of cholelithiasis (aHR = 1.76, 95% C.I. 1.20-2.58, p = 0.003) and peptic ulcer disease (aHR = 1.87, 95% C.I. 1.52-2.29, p < 0.001) had significantly higher risk of osteoporosis. We propose that this correlation may be related to increased hematopoietic stress, increased consumption of nitric oxide (NO) by hemolysis, and the inhibitory effects of iron supplements on osteogenesis through the receptor activator of nuclear factor κB ligand (RANKL)/Osteoprotegerin pathway and the Runt-related transcription factor 2 (RUNX2) factor. Our findings suggest that patients with hemolytic anemia are at a higher risk of developing osteoporosis, and it would be in the patient's best interest for physicians to be aware of this potential complication and offer preventative measures.

The risk of fibromyalgia in patients with iron deficiency anemia: a nationwide population-based cohort study.

Since iron is essential for neurotransmitter synthesis, decreased iron stores might lead to reduced production of biogenic amines which phenomenon was shown in Fibromyalgia (FM) patients. The aims are to investigate the association of iron deficiency anemia (IDA) and FM and to find the effects of different interventions. We conducted a study using the Taiwan National Health Insurance Research Database. The IDA cohort consisted of 13,381 patients with newly diagnosed IDA between 2000 and 2008. Each patient with IDA was frequency-matched with one people without IDA, by sex, age and index year. The Cox proportional hazards regression analysis was conducted to estimate the association between IDA and FM risk. The event was the occurrence of FM. The overall incidence density rate of FM in the IDA cohort was higher than in the non-IDA cohort with a multivariable Cox proportional hazards model measured adjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.13-1.25). When using non-IDA group as reference, we compared with different therapies for IDA. The adjusted HRs of FM were 1.38 (95% CI = 1.30-1.47), 1.10 (95% CI = 1.03-1.16), 1.18 (95% CI = 0.98-1.43) and 0.73 (95% CI = 0.58-0.90) for IDA patient without therapy, iron supplement alone, blood transfusion alone and both iron supplement and blood transfusion respectively. Our results suggest IDA is associated with an increased risk of FM. All patients should have iron supplementation both to correct anemia and replenish body stores.

How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight.

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

The predisposing factors of AKI for prophylactic strategies in burn care.

BACKGROUND: Acute kidney injury (AKI) is one of the most severe complications of burn injury. AKI with severe burn injury causes high mortality. This study aims to investigate the incidence of and predisposing factors for AKI in burn patients. METHODS: This is a single-center, retrospective, descriptive criterion standard study conducted from June 27, 2015, to March 8, 2016. We used Kidney Disease Improving Global Outcomes criteria to define and select patients with AKI. The study was conducted by recruiting in hospital patients who suffered from the flammable cornstarch-based powder explosion and were treated under primary care procedures. A total of 49 patients who suffered from flammable dust explosion-related burn injury were enrolled and admitted on June 27, 2015. The patients with more than 20% total body surface area of burn were transferred to the intensive care unit. Patients received fluid resuscitation in the first 24 hours based on the Parkland formula. The primary measurements were the incidence of and predisposing factors for AKI in these patients. Demographic characteristics, laboratory data, and inpatient outcomes were also evaluated. The incidence of AKI in this cohort was 61.2% (n = 30). The mortality rate was 2.0% (n = 1) during a 59-day follow-up period. The multivariate analysis revealed inhalation injury (adjusted OR = 22.0; 95% CI [1.4-358.2]) and meeting ≥3 American Burn Association (ABA) sepsis criteria (adjusted OR = 13.7; 95% CI [1.7-110.5]) as independent risk factors for early advanced AKI. CONCLUSIONS: The incidence rate of AKI was higher in this cohort than in previous studies, possibly due to the flammable dust explosion-related burn injury. However, the mortality was lower than that expected. In clinical practice, indicators of inflammation, including ABA sepsis criteria may help in predicting the risk of AKI in patients with burn injury.

Discordance of vancomycin minimum inhibitory concentration for methicillin-resistant Staphylococcus aureus at 2 µg/mL between Vitek II, E-test, and Broth Microdilution.

BACKGROUND: Vancomycin, the first line antibiotic for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, is often administered inappropriately when MIC is greater than 2 µg/mL, including 'susceptible' strains. This study assessed the discordance of vancomycin minimum inhibitory concentration (MIC) for methicillin-resistant Staphylococcus aureus (MRSA). METHODS: In total, 229 MRSA isolates from blood cultures collected between 2009 and 2015 at a tertiary hospital in Taiwan were examined. The MICs of vancomycin were measured using Vitek 2, E-test, and standard broth microdilution at the level of 2 µg/mL. RESULTS: The geometric mean of the MICs of hospital-acquired MRSA was higher than that of community-acquired MRSA (P < 0.001), with the exact agreement rates (with broth microdilution) at 2 µg/mL being 53.6% in Vitek 2 and 86.7% in E-test. Overall, E-test (98.1%) had more categorical accordance than did Vitek 2 (94.0%; P = 0.026). Vitek 2 had a tendency to overestimate MRSA in high-MIC isolates, whereas E-test inclined underestimation in low-MIC isolates. Surprisingly, the discordance rates of MRSA vancomycin MICs were higher in hospital-acquired isolates (13.3%-17.0%) than in community-acquired isolates (6.2%-7.0%). CONCLUSION: The Infectious Diseases Society of America recommends the use of alternative antimicrobial agents when vancomycin MIC is ≥ 2 µg/mL; in this study, only 53.6% of the isolates tested using Vitek 2 showed a high MIC in the broth microdilution method. Accurate identification of the resistance profile is a key component of antimicrobial stewardship programs. Therefore, to reduce inappropriate antibiotic use and mitigate the emergence of resistant strains, we recommend using complementary tests such as E-test or Broth microdilution to verify the MIC before administering second-line antibiotics. STRENGTHS: (1) We compared the categorical agreement between different methods measuring MRSA MICs level. (2) Physicians should incorporate this information and consider a complementary test to verify the appropriateness of the decision of shifting vancomycin to second-line antibiotic treatment to improve patients' prognosis. (3) MRSA-vancomycin MICs at a cutoff of 2 µg/mL obtained using Vitek II exhibited a higher sensitivity level and negative predictive value than those obtained using E-test in the prediction of categorical agreement with standard broth microdilution. LIMITATION: (1) Our research was based on a single hospital-based study. (2) The MRSA strains in this study were stored for more than 12 months after isolation. (3) We did not collect information on clinical prognosis.

Development of high-growth influenza H7N9 prepandemic candidate vaccine viruses in suspension MDCK cells.

BACKGROUND: Influenza vaccine manufacturers traditionally use egg-derived candidate vaccine viruses (CVVs) to produce high-yield influenza viruses for seasonal or pandemic vaccines; however, these egg-derived CVVs need an adaptation process for the virus to grow in mammalian cells. The low yields of cell-based manufacturing systems using egg-derived CVVs remain an unsolved issue. This study aimed to develop high-growth cell-derived CVVs for MDCK cell-based vaccine manufacturing platforms. METHODS: Four H7N9 CVVs were generated in characterized Vero and adherent MDCK (aMDCK) cells. Furthermore, reassortant viruses were amplified in adherent MDCK (aMDCK) cells with certification, and their growth characteristics were detected in aMDCK cells and new suspension MDCK (sMDCK) cells. Finally, the plaque-forming ability, biosafety, and immunogenicity of H7N9 reassortant viruses were evaluated. RESULTS: The HA titers of these CVVs produced in proprietary suspension MDCK (sMDCK) cells and chicken embryos were 2- to 8-fold higher than those in aMDCK cells. All H7N9 CVVs showed attenuated characteristics by trypsin-dependent plaque assay and chicken embryo lethality test. The alum-adjuvanted NHRI-RG5 (derived from the fifth wave H7N9 virus A/Guangdong/SP440/2017) vaccine had the highest immunogenicity and cross-reactivity among the four H7N9 CVVs. Finally, we found that AddaVax adjuvant improved the cross-reactivity of low pathogenic H7N9 virus against highly pathogenic H7N9 viruses. CONCLUSIONS: Our study indicates that cell-derived H7N9 CVVs possessed high growth rate in new sMDCK cells and low pathogenicity in chicken embryo, and that CVVs generated by this platform are also suitable for both cell- and egg-based prepandemic vaccine production.

Cost-drivers of medical expenses in burn care management.

BACKGROUND: Profound differences exist in the cost of burn care globally, thus we aim to investigate the affected factors and to delineate a strategy to improve the cost-effectiveness of burn management. METHODS: A retrospective analysis of 66 patients suffering from acute burns was conducted from 2013 to 2015. The average age was 26.7 years old and TBSA was 42.1% (±25.9%). We compared the relationship between cost and clinical characteristics. RESULTS: The estimated cost of acute burn care with the following formula (10,000 TWD) = -19.80 + (2.67 × percentage of TBSA) + (124.29 × status of inhalation injury) + (147.63 × status of bacteremia) + (130.32 × status of respiratory tract infection). CONCLUSION: The majority of the cost were associated with the use of antibiotics and burns care. Consequently, it is crucial to prevent nosocomial infection in order to promote healthcare quality and reduce in-hospital costs.