The epidemiology and prognostic factors of mortality in critically ill children with acute kidney injury in Taiwan.

The incidence of acute kidney injury (AKI) in critically ill children varies among countries. Here we used claims data from the Taiwanese National Health Insurance program from 2006 to 2010 to investigate the epidemiological features and identify factors that predispose individuals to developing AKI and mortality in critically ill children with AKI. Of 60,338 children in this nationwide cohort, AKI was identified in 850, yielding an average incidence rate of 1.4%. Significant independent risk factors for AKI were the use of extracorporeal membrane oxygenation, mechanical ventilation or vasopressors, intrinsic renal diseases, sepsis, and age more than 1 year. Overall, of the AKI cases, 46.5% were due to sepsis, 36.1% underwent renal replacement therapy, and the mortality rate was 44.2%. Multivariate analysis showed that the use of vasopressors, mechanical ventilation, and hemato-oncological disorders were independent predictors of mortality in AKI patients. Thirty-two of the 474 patients who survived had progression to chronic kidney disease or end-stage renal disease. Thus, although not common, AKI in critically ill children still has a high mortality rate associated with a variety of factors. Long-term close follow-up to prevent progressive chronic kidney disease in survivors of critical illnesses with AKI is mandatory.

Mapping of IgE and IgG4 antibody-binding epitopes in Cyn d 1, the major allergen of Bermuda grass pollen.

BACKGROUND: Bermuda grass pollen (BGP) is an important seasonal aeroallergen worldwide which induces allergic disorders such as allergic rhinitis, conjunctivitis and asthma. Cyn d 1 is the major allergen of BGP. This study is aimed to map human IgE and IgG(4) antibody-binding sequential epitopes on Cyn d 1 by dot immunoblotting. METHODS: Synthetic peptides (10-mers; 5 overlapping residues) spanning the full length of Cyn d 1 were used for dot immunoblotting to map human IgE and IgG(1-4) antibody-binding regions with sera from BGP-allergic patients. Synthetic peptides with more overlapping residues were used for further mapping. Essential amino acids in each epitope were examined by single amino acid substitution with alanine. Peptides with sequence polymorphism of epitopes of Cyn d 1 were also synthesized to extrapolate their differences in binding capability. RESULTS: Four major IgE-binding epitopes (peptides 15(-1), 21, 33(-2) and 35(+1), corresponding to amino acids 70-79, 101-110, 159-167 and 172-181) and 5 major IgG(4)-binding epitopes (peptides 15(-1), 30(-2), 33(-2), 35(+1) and 39, corresponding to amino acids 70-79, 144-153, 159-167, 172-181 and 192-200) were identified. They are all located on the surface of the simulated Cyn d 1 molecule, and three of them are major epitopes for both IgE and IgG(4). Their critical amino acids were all characterized. Major epitopes for human IgG(1) to IgG(4) are almost identical. CONCLUSIONS: This is the first study to map the sequential epitopes for human IgE and IgG(4) subclasses in Cyn d 1. It will be helpful for future development in immunotherapy and diagnosis.

Relationship among asthma knowledge, behavior management and social adaptation in school-age children with asthma in Taiwan.

This study examined the relationships between asthma knowledge, behavior management, and social adaptation among school-age children with asthma. A total of 210 school-age asthmatic children and their parents were recruited from a medical hospital in Taiwan. The children completed asthma knowledge and behavior management questionnaires, and their parents completed the Child and Adolescent Adjustment Profile. There was a statistically significant positive correlation between behavior management and social adaptation among asthmatic children. Asthma knowledge and behavior management were positively associated but did not correlate with children's social adaptation. The behavior management of the children acted as a predictor of their social adaptation. These findings suggest that efforts to raise children's asthma knowledge will benefit these individuals in terms of behavior management. The introduction of asthma behavior management plans could facilitate the social adaptation of asthmatic children and, in particular, increase their independence and reduce their withdrawal as well as enhance their self-confidence and self-esteem.

Occurrence of human cytomegalovirus glycoprotein B genotypes in immunocompetent and immunosuppressed Taiwanese patients.

OBJECTIVES: To investigate the differences of genotypic distributions among isolates between immunosuppressed and immunocompetent patients in a Taiwanese population. METHODS: Human cytomegalovirus (HCMV) isolates from 76 patients with adequate chart data were analyzed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to define gB genotypes which include gB1 to gB4. The clinical data of the 76 patients were retrospectively collected by chart review and classified into an immunosuppressed (n = 32) or immunocompetent (n = 44) group. RESULTS: Among the 32 immunosuppressed patients, the most commonly identified HCMV genotypes were gB1 (27/32, 84.3%) and gB3 (4/32, 12.5%). 59.1% (26/44) of the immunocompetent patients were infected by gB1 while 38.6% (17/44) of them were infected by gB3. The frequency of gB1 infection in the immunosuppressed group was significantly higher than that in the immunocompetent group (p = 0.025). However, there was no statistically significant difference between gB1 and gB3 distributions by clinical diagnosis within each group. CONCLUSIONS: Only gB1 and gB3 genotypes were identified in this Taiwanese population. Although there is no significant difference between clinical diagnosis and gB genotyping, gB1 infection is significantly more predominant in immunosuppressed patients.

Associations Between Psychiatric Disorders and Enuresis in Taiwanese Children: A National Population-Based Study.

BACKGROUND: Psychiatric disorders such as attention-deficit/hyperactivity disorder may negatively impact drug compliance and the prognosis of enuresis. However, existing studies regarding associations between lifetime psychiatric disorders and childhood enuresis are primarily from Western countries, and studies from Taiwan are lacking. METHODS: We conducted a population-based retrospective cohort analysis using the Taiwan Longitudinal Health Insurance Database 2010. A total of 1,146 children with enuresis (ICD-9-CM code: 307.6) and 4,584 randomly selected sex- and age-matched controls were identified between January 1, 1997 and December 31, 2011. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the development of psychiatric disorders in the children with enuresis. RESULTS: Enuresis was more common in the younger children, and the rate was significantly higher in boys (58.7%) than in girls (41.3%). A total of 171 patients (14.9%) in the enuresis group had at least one psychiatric diagnosis vs 259 (5.7%) in the control group (p<0.001). Multivariate analysis showed that the presence of enuresis increased the odds of developing major depressive/dysthymic disorder (OR=2.841, 95% CI: 1.619, 4.987), attention-deficit/hyperactivity disorder (OR=3.156, 95% CI: 2.446, 4.073), autism spectrum disorder (OR=2.468, 95% CI: 1.264, 4.822), anxiety disorders (OR=3.113, 95% CI: 2.063, 4.699), intelligence disability (OR=3.989, 95% CI: 2.476, 6.426), disruptive behavior disorders (OR=3.749, 95% CI: 1.756, 8.004), and tic disorder (OR=2.660, 95% CI: 1.642, 4.308). CONCLUSION: Children with enuresis are likely to have psychiatric disorders, and physicians should consider this during their evaluation.

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III, open label, single-arm study.

BACKGROUND: Quadrivalent influenza vaccines are particularly valuable during seasons in which a mismatch occurs between the predicted influenza B lineage for the trivalent influenza vaccine and the circulating strain. This study evaluated the immunogenicity and safety of a quadrivalent inactivated influenza vaccine AdimFlu-S manufactured in Taiwan for the 2016-2017 influenza season in healthy children. METHODS: A total of 174 healthy children aged 3 to 17 years old were separated into 3 groups (Group A: 3-8 years old, vaccine naïve; Group B: 3-8 years old, vaccine non-naïve; Group C: 9-17 years old, any vaccine status). Sera was collected pre and post vaccination for each participant. A hemagglutination inhibition (HAI) assay was utilized to calculate geometric mean titer (GMT), seroprotection rate, and seroconversion rate. RESULTS: All enrolled participants completed the study. For the four vaccine strains four weeks after the last vaccination, geometric mean titer ratios (GMTRs) were between 2.9 and 20.9, seroconversion rates were between 42.9% and 90.9%, and seroprotection rates were all above 96.4%. This achieved all immunogenicity endpoints and fulfilled the criteria of the European Medical Agency's Committee for Medicinal Products for Human Use (CHMP). No serious adverse events (AEs) were reported during the follow-up period of 6 months. CONCLUSION: This quadrivalent influenza vaccine is demonstrated to be well tolerated and displays robust immunogenicity for each influenza strain. This could potentially improve protection against the antigenically distinct B/Yamagata and B/Victoria lineages.

Recommendations for the use of Japanese encephalitis vaccines.

Japanese encephalitis (JE) is a mosquito-borne viral infection which is prevalent in Taiwan. The virus circulates in an enzootic cycle in pigs which serve as amplifying hosts. Outbreaks typically occur during summer. A universal vaccination program using 4-shot mouse brain-derived inactivated vaccine has successfully controlled JE epidemics in Taiwan since 1968. More than 90% of JE cases in recent years were older than 20 years in Taiwan. Because of several drawbacks, mouse brain-derived vaccine has been replaced by newer generation JE vaccines, including inactivated Vero cell-derived vaccine and live chimeric vaccine. The present article describes the recommendations in Taiwan for the use of new JE vaccines and the schedules for shifting between different JE vaccines.

Associations between environmental heavy metal exposure and childhood asthma: A population-based study.

BACKGROUND/PURPOSE: The health risks of environmental heavy metals have been of concern are well known. The greater likelihood of heavy metal contamination in the physical environment increases the risk of asthma, especially in children. This cross-sectional, population-based study sought to investigate associations between heavy metal exposure and childhood asthma or wheezing. METHODS: Data from 5866 subjects, stratified into age groups of 2-5, 6-11, and 12-15 years, from the National Health and Nutrition Examination Survey 2007-2012 conducted by the Centers for Disease Control and Prevention were analyzed retrospectively. The primary outcome was active asthma. Variables included demographics, anthropometric, and clinical data. Univariate and multivariate logistic regression analyses were used to identify associations between blood heavy metal concentrations and adjusted odds (aORs) of active asthma. RESULTS: Higher concentration of blood lead was associated with higher adjusted odds of having asthma (aOR = 1.08, 95% CI = 1.00-1.16), but no significant effect was shown for current wheezing or whistling. Age-stratified analysis showed that higher blood lead concentration was associated with higher risk for active asthma (aOR = 1.24, 95% CI = 1.08-1.42) and current wheezing or whistling (aOR = 1.19, 95% CI = 1.04-1.38) in the 6-11 years age group, while higher blood mercury concentration was associated with lower risk of current wheezing or whistling (aOR = 0.95, 95% CI = 0.90-0.99). The medium concentration of blood lead was associated with decreased risks of current wheezing or whistling (aOR = 0.54, 95% CI = 0.30-0.96) in the 2-5 years age group. CONCLUSION: Higher concentrations of blood lead are associated with higher odds of asthma in children aged 2-15 years.

Immunogenicity and safety of an inactivated enterovirus A71 vaccine in children 3-6 years and 2-35 months of age- an open-label, randomized phase IIb clinical trial.

BACKGROUND: Enterovirus A71 (EV-A71) infection can cause severe debilitating complications and even death in young children. The immunogenicity and safety of an inactivated whole EV-A71 virus vaccine were assessed in children 2 months to 6 years of age. METHODS: This was an open-label, multi-center and randomized phase IIb study, which divided into part A and B. In part A, children 36 months to 6 years of age were enrolled and randomized into 3 groups, receiving 0.5 µg total viral protein (TP) with adjuvant Al(OH)3, 1.0 µg TP with Al(OH)3 or 1.0 µg TP only. Two doses of vaccines were administered at a 28-day interval and blood was taken before immunization, at week 4, 8, 28 and 52 (optional) for virus neutralization assay. Safety profiles were also monitored. After safety profiles had shown no concerns, children 2 months to 35 months of age (part B) were subsequently enrolled following the same protocol. RESULTS: A total of 135 children completed two doses of immunization, including 58 in part A and 77 in part B. Both adjuvanted 0.5 µg and 1.0 µg TP elicited significant raise of neutralizing antibody titers and seroconversion rate was up to 93.75-100.0% after 2 doses of immunization. Adjuvanted 1.0 µg TP induced higher titers of neutralizing antibodies than adjuvanted 0.5 µg TP. By contrast, non-adjuvanted 1.0 µg TP was not immunogenic. No major adverse events were reported. CONCLUSIONS: This EV-A71 vaccine containing adjuvant is immunogenic and safe in children 2 months to 6 years of age. CLINICAL TRIALS REGISTRATION: NCT03268083.

Role of intravenous immunoglobulin therapy in the survival rate of pediatric patients with acute myocarditis: A systematic review and meta-analysis.

The treatment of pediatric myocarditis is controversial, and the benefits of intravenous immunoglobulin (IVIG) are inconclusive due to limited data. We searched studies from PubMed, MEDLINE, Embase, and Cochrane Library databases since establishment until October 1st, 2018. Thirteen studies met the inclusion criteria. We included a total of 812 patients with IVIG treatment and 592 patients without IVIG treatment. The meta-analysis showed that the survival rate in the IVIG group was higher than that in the non-IVIG group (odds ratio = 2.133, 95% confidence interval (CI): 1.32-3.43, p = 0.002). There was moderate statistical heterogeneity among the included studies (I2 = 35%, p = 0.102). However, after adjustment using Duval and Tweedie's trim and fill method, the point estimate of the overall effect size was 1.40 (95% CI 0.83, 2.35), which became insignificant. Moreover, the meta-regression revealed that age (coefficient = -0.191, 95% CI (-0.398, 0.015), p = 0.069) and gender (coefficient = 0.347, 95% CI (-7.586, 8.279), p = 0.93) were not significantly related to the survival rate. This meta-analysis showed that IVIG treatment was not associated with better survival. The use of IVIG therapy in acute myocarditis in children cannot be routinely recommended based on current evidence. Further prospective and randomized controlled studies are needed to elucidate the effects of IVIG treatment.

Group B Streptococcal infection in neonates and colonization in pregnant women: An epidemiological retrospective analysis.

BACKGROUND: Group B Streptococcus (GBS) infection is one of the major causes of neonatal morbidity and mortality. Universal GBS screening with intrapartum antibiotic prophylaxis (IAP) in pregnant women were initiated in 2012 in Taiwan. This study aimed to analyze the most recent maternal GBS colonization rate and the changes in neonatal GBS infection rate from 2011 to 2016. METHODS: All pregnant women and their live born neonates between January 2011 and June 2016 were retrospectively reviewed. Whether GBS screening was done, screening results, presence of risk factors, the use of antibiotics, and neonatal outcome were analyzed. In addition, hospitalized neonates diagnosed with GBS infections were retrieved for comparison of early onset disease (EOD) (<7 days) and late onset disease (LOD) (≥7 days). RESULTS: A total of 9535 women delivered babies during the study period. The maternal GBS screening rate was 71.0% and the colonization rate was 22.6%. The overall neonatal invasive GBS infection rate was 0.81 per 1000 live births and the vertical transmission rate was 1.2%. After 2012, the invasive neonatal GBS infection rate declined from 1.1-1.6‰ to 0.6-0.7‰ in 2014 and thereafter, the GBS EOD incidence rate declined from 2.8‰ to 0.0-0.6‰, but the LOD incidence rate remained approximately 0.7‰. Infants with EOD had strong association with obstetric risk factors. CONCLUSIONS: Taiwan's universal GBS screening with IAP program reduced the incidence rate of neonatal GBS EOD to be lower than 1‰ after 2012. Pediatricians still should pay attention to infants with GBS LOD since its incidence rate remained unchanged.

Viral etiologies of acute respiratory tract infections among hospitalized children - A comparison between single and multiple viral infections.

BACKGROUND: Acute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed. METHODS: We retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared. RESULTS: A total of 442 patients were enrolled. Patients with positive viral detection (N = 311) had a significantly lower rate of leukocytosis (p = 0.03), less evidence of bacterial infection (p = 0.004), and shorter duration of hospitalization (p = 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups. The most commonly identified virus was human rhinovirus. About 27% (n = 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was independently associated with multiple viral infections (p = 0.022), respiratory syncytial virus (RSV) infection (p = 0.001) and longer hospitalization duration (p = 0.011). CONCLUSION: Multiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.

Neonatal sublingual vaccination with Salmonella proteins and adjuvant cholera toxin or CpG oligodeoxynucleotides induces mucosal and systemic immunity in mice.

OBJECTIVES: Salmonella enteritidis is one of the most common enteric pathogens that cause acute gastroenteritis. A vaccine that can induce systemic and mucosal immune responses by a simple, noninvasive pathway and provide protection against this mucosal pathogen is needed. MATERIALS AND METHODS: Newborn BALB/c mice were sublingually vaccinated daily for the first 3 days with sonicated Salmonella proteins (SSP) only, or SSP combined with adjuvant CpG or cholera toxin (CT). A booster vaccination was given 7 weeks after the last treatment. Serum and saliva antibody responses, cytokine profiles of spleen cells, survival rate, and intestinal morphology after live S enteritidis challenge were investigated. RESULTS: Saliva-specific secretory IgA (SIgA) antibody responses were markedly enhanced by neonatal sublingual vaccination with SSP together with adjuvant CpG or CT. Whereas vaccination with SSP and CpG enhanced spleen cell interferon-gamma production and serum-specific IgG2a antibody responses, vaccination with SSP and CT increased spleen cell interleukin (IL)-4, IL-5, IL-6, and interferon-gamma production and serum-specific IgG1 and IgG2a antibody responses. Vaccination with SSP and CpG or CT protected against intestinal necrosis and was associated with a higher survival rate after oral challenge with live S enteritidis. The vaccinated mice with higher specific IgG and saliva-specific secretory IgA antibody levels had a better survival rate. CONCLUSIONS: Neonatal sublingual vaccination with adjuvant CpG or CT can induce both mucosal and systemic immunity and may play a crucial role in protection against enteric pathogens.

The role of eosinophil cationic protein in patients with Mycoplasma pneumoniae infection.

BACKGROUND: To study the role played by eosinophil cationic protein (ECP) in patients with Mycoplasma pneumonia infection. METHODS: Pediatric patients aged 4 to 14 years old were divided into 3 groups, each consisting of 30 patients. Group 1 comprised patients with known M. pneumoniae infection. Group 2 comprised patients with asthma who were in a stable condition with no infection, acute asthma exacerbation or steroid use in the last 2 months. Group 3 consisted of healthy children and was designated the control group. The level of ECP in patients' serum was measured by an ECP radioimmunoassay kit. RESULTS: There were 90 children enrolled in this study; 59 (65.56%) were boys and 31 (34.44%) were girls. Mean serum ECP levels between males and females was not significantly different (p = 0.544). The variance of serum ECP levels decreased as patient age increased, but there was no relationship between serum ECP level and patient age (gamma = 0.118, p = 0.267). Serum ECP levels were similar in both the M. pneumoniae-infected and asthma groups; serum ECP levels in the control group were less than the levels seen in the other 2 groups. The difference in serum ECP levels among the 3 groups was statistically significant (p < 0.001). CONCLUSION: Both the children who had M. pneumoniae infection and the children with asthma had significantly increased serum ECP levels compared to normal healthy children. The elevated ECP levels found in the serum of patients with M. pneumoniae infection may be associated with damage to the respiratory epithelium and accelerated hypersensitivity in the respiratory system. Decreasing the serum level of ECP may potentially be a method of relieving symptoms in patients with M. pneumoniae infection. Additional studies are warranted to further validate this conclusion.

High prevalence of IgE sensitization against house dust mites in pregnant women.

There is an increase in prevalence and financial burden of childhood atopic disorders in recent years. Understanding allergic conditions of pregnant women is important for developing strategies for prevention and management of allergy-related diseases. However, little is currently known about the atopic conditions in pregnant women.The sera from 46 pregnant women were analyzed for allergen-specific IgE antibodies using the Optigen assay and SDS-PAGE immunoblot analysis.Results from the Optigen assay showed that 20 (43%) of the 46 serum samples analyzed demonstrated IgE reactivity against mite p (Dermatophagoides pteronyssinus) (95%), mite f (D farinae) (95%), house dust (60%), cat (25%), shrimp (20%), crab (15%), cockroach (10%), dog (5%), latex (5%), willow black (5%), and timothy grass (5%). Nineteen of the 20 Optigen-positive sera demonstrated IgE reactivity against both the house dust mites D pteronyssinus and D farina, with 10 of them having a high IgE CLA class value of 4. IgE reactivity to the house dust mite D pteronyssinus was confirmed in SDS-PAGE-immunoblots, which correlated well with the intensity of IgE-binding to the 15-kDa D pteronyssinus component and to the purified recombinant Der p 2 major house dust mite allergen.A high prevalence of IgE sensitization against house dust mites during pregnancy is noted, which is worthy of clinical attention. Children of IgE-sensitized mothers should be closely monitored for development of allergenic disorders.

Characteristics of Chlamydia trachomatis infection in hospitalized infants with lower respiratory tract infection.

BACKGROUND AND PURPOSE: To study the epidemiology, presentation and laboratory findings of Chlamydia trachomatis pneumonia in hospitalized infants younger than 6 months. METHODS: Between January 2001 and December 2005, infants younger than 6 months admitted to the children's medical center of Taipei Veterans General Hospital with the diagnosis of acute bronchiolitis, bronchopneumonia or pneumonia were prospectively studied. Chest radiograph findings were reviewed in all patients. Basic laboratory examinations performed included white blood cell count and eosinophil count. C. trachomatis was detected via enzyme-linked immunosorbent assay antigen test and the titers of immunoglobulin G and immunoglobulin M by indirect immunoperoxidase assay. RESULTS: A total of 60 infants, 32 males and 28 females, were included. C. trachomatis infection was detected in 30% of patients (18/60). The median age was 2.5 months (range, birth to 6 months). Fever was not detected in 72% of patients (13/18). Only 22% (4/18) of these patients had the characteristic staccato cough. The mean duration of symptoms before admission was 8 days (range, 1 day to 2 months). Rhinorrhea was a prodromal symptom in 67% (12/18) of patients, with a mean pre-onset duration of 7 days (range, 1 to 14 days). Eighty three percent (15/18) of the patients had tachypnea, with a mean duration of 3.2 days (range, 1 to 7 days). Conjunctivitis was noted before admission in 6 patients (33%). Only peripheral eosinophils showed statistically significant difference between Chlamydia-positive and -negative disease (p=0.046), and may be clinically useful in cases of suspected C. trachomatis infection. Mixed infection with other pathogens including adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, cytomegalovirus and Streptococcus pneumoniae was found in 27% (5/18) of patients. CONCLUSIONS: C. trachomatis is not infrequent and plays an important role in infants younger than 6 months old hospitalized due to lower respiratory tract infection.

Heat-killed cells of lactobacilli skew the immune response toward T helper 1 polarization in mouse splenocytes and dendritic cell-treated T cells.

It is believed that probiotics play an important role for the health of the host, including modulation of immune responses. Most studies have focused on the immunomodulatory effects of viable cells of lactic acid bacteria; however, we investigated those of heat-killed cells of lactic acid bacteria in this study. We first observed the effects on immune functions via stimulating splenocytes with three heat-killed Lactobacillus strains. Furthermore, we also investigated the effect of mouse dendritic cells (DCs) treated with these heat-killed Lactobacillus strains on T cell responses. The results showed that these Lactobacillus strains were able to stimulate cell proliferation and interleukin (IL)-10, IL-12 p70, and interferon (IFN)-gamma production but not transforming growth factor (TGF)-beta in splenocytes. In addition, these heat-killed Lactobacillus strains also stimulated high-level secretion of IL-12 p70 in DCs and switched T cells to T helper (Th) 1 immune responses, as evidenced by the elevated secretion of IFN-gamma but not IL-5, IL-13, and TGF-beta. These results showed that lactobacilli play a potentially important role in modulating immune responses and allergic reactions.

Risk of cancer in patients with genital warts: A nationwide, population-based cohort study in Taiwan.

BACKGROUND: Condyloma acuminata currently affects around 1% of sexually active adults, and its incidence is increasing. The coexistence of genital warts (GW) and certain cancers and an association between human papillomavirus (HPV) and various malignancies have been reported. Therefore, we conducted this large national study to analyze the risk of malignancies among men and women with GW in Taiwan. METHODS AND FINDINGS: Between January 2000 and December 2013, approximately 3 million patients were reported to the National Health Insurance Research Database of Taiwan. Of these patients, 21,763 were diagnosed with GW. In the same time period, a total of 213,541 cancer cases were reported to the registry, of which 1002 were recorded among patients with GW. The age-specific incidence rates of GW and standardized incidence ratios (SIRs) of malignancies compared to the general population were calculated. Women acquired GW earlier than men, with a mean age at diagnosis of 32.63±12.78 years. The highest incidence rate for both genders peaked at 20-29 years. Of the 1002 patients with GW and malignancies, the SIR was 1.95 (95%CI 1.83-2.07). The most markedly increased risk was found for HPV-related cancers, with a SIR of 9.74 (95%CI 3.70-15.77). Significantly elevated risks were also noted for smoking-related cancers, anogenital cancers, cervix in situ, colon, rectum, lung, kidney, and prostate cancers. Most cancers developed within 10 years after the diagnosis of GW. CONCLUSIONS: Patients with GW have an increased risk of HPV-related cancers, especially anogenital malignancies in Taiwan. The elevated risk of other cancers highlights differences in exposure and risk factors among patients with GW compared to the general population. Cancer screening and HPV vaccination programs should be emphasized for at-risk patients.

Recent trends in prescribing antibiotics for acute tonsillitis in pediatric ambulatory care in Taiwan, 2000-2009: A nationwide population-based study.

BACKGROUND/PURPOSE: Acute tonsillitis is the leading diagnosis in pediatric ambulatory care, and group A beta-hemolytic streptococcus is the main reason for antibiotic prescriptions in patients with acute tonsillitis. The aim of this study was to analyze trends in prescribing antibiotics and to investigate the prescription patterns for acute tonsillitis in pediatric ambulatory care in Taiwan from 2000 to 2009. METHODS: Data on children younger than 18 years with a primary diagnosis of acute tonsillitis were retrieved from the National Health Insurance Research Database of Taiwan from 2000 to 2009. Concomitant bacterial infections were excluded. Sex, age, seasonality, location, level of medical institution, and physician specialty were analyzed. Annual and monthly changes in antibiotic prescriptions and classification were also evaluated. RESULTS: A total of 40,775 cases were enrolled, with an overall antibiotic prescription rate of 16.8%. There was a remarkable decline in the antibiotic prescription rates for tonsillitis from 28.4% in 2000 to 10.9% in 2009. Factors associated with a higher prescription rate included older age, visits from eastern Taiwan, medical centers, and nonpediatrician physicians. Otolaryngologists had higher antibiotic prescription rate, whereas pediatricians had the lowest (21.9% vs. 11.6%). The rates of obtaining throat cultures were low although the culture performing rate in the medical centers was significantly higher (12.3%, p < 0.001). CONCLUSION: From 2000 to 2009, there was a remarkable decline in the antibiotic prescription rates for tonsillitis. Further studies to evaluate diagnostic tools such as rapid antigen detection tests or throat cultures to decrease antibiotic prescriptions are warranted.

Clinical analysis of fever of unknown origin in children: A 10-year experience in a northern Taiwan medical center.

BACKGROUND: Fever of unknown origin (FUO) was first described in 1961 as fever >38.3°C for at least 3 weeks with no apparent source after 1 week of investigations in the hospital. Infectious disease comprises the majority of cases (40-60%). There is no related research on FUO in children in Taiwan. The aim of this study is to determine the etiologies of FUO in children in Taiwan and to evaluate the relationship between the diagnosis and patient's demography and laboratory data. METHODS: Children under 18 years old with fever >38.3°C for >2 weeks without apparent source after preliminary investigations at Taipei Veterans General Hospital during 2002-2012 were included. Fever duration, symptoms and signs, laboratory examinations, and final diagnosis were recorded. The distribution of etiologies and age, fever duration, laboratory examinations, and associated symptoms and signs were analyzed. RESULTS: A total of 126 children were enrolled; 60 were girls and 66 were boys. The mean age was 6.7 years old. Infection accounted for 27.0% of cases, followed by undiagnosed cases (23.8%), miscellaneous etiologies (19.8%), malignancies (16.6%), and autoimmune disorders (12.7%). Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were the most commonly found pathogens for infectious disease, and Kawasaki disease (KD) was the top cause of miscellaneous diagnosis. CONCLUSIONS: Infectious disease remains the most common etiology. Careful history taking and physical examination are most crucial for making the diagnosis. Conservative treatment may be enough for most children with FUO, except for those suffering from malignancies.