Kuang-Hung Hsu

Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease

BACKGROUND In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. METHODS We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. FINDINGS Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 [95% CI 2.6-60.1], p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p=0.003). INTERPRETATION EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.

Use of the Antral Follicle Count to Predict the Outcome of Assisted Reproductive Technologies

OBJECTIVE To evaluate the predictive value of the antral follicle count in patients undergoing assisted reproductive technologies (ARTs). DESIGN Prospective study. SETTING Tertiary care institutional hospital. PATIENT(S) Consecutively seen patients undergoing ARTs such as IVF-ET, gamete intrafallopian transfer, and tubal embryo transfer (TET). INTERVENTION(S) The ovarian antral follicle number was determined by transvaginal ultrasonography on the first or second menstrual day, before the administration of gonadotropins, in patients undergoing ARTs. MAIN OUTCOME MEASURE(S) Ovulation induction was accomplished with the use of GnRH agonist down-regulation combined with FSH and menotropin stimulation. Gamete intrafallopian transfer or TET was performed in patients with patent fallopian tubes, and IVF-ET was undertaken in the remaining patients. Analysis of variance and Mantel-Haenszel monotonic test for trends were used for data analysis. RESULT(S) A total of 149 treatment cycles for 130 couples were performed during the study period. The procedures performed included 89 ETs, 26 gamete intrafallopian transfers, 13 TET cycles, and 21 incomplete cycles (9 poor responders, 6 failed retrievals, and 6 nonfertilization cycles). All treatment cycles were divided into three groups according to the number of antral follicles (i.e., < or = 3, 4-10, and > or = 11) to evaluate the influence of various factors. The antral follicle count correlated significantly with patient age, day 3 serum FSH level, use of gonadotropins, serum estradiol concentration, number of oocytes retrieved, and, later, number of oocytes or embryos transferred. The group of patients who had a lower antral follicle count also had a significantly higher rate of cycle cancellation compared with the other two groups (68.8% vs. 5.3% and 0, respectively). No pregnancies occurred in the low antral follicle count group, whereas there was a trend toward an increasing number of pregnancies per attempt as the number of antral follicles increased (0, 23.7%, and 36.8%, respectively). CONCLUSION(S) It is easy to determine the number of antral follicles with a diameter of 2-5 mm on the first or second day of menstruation, or just before the administration of exogenous gonadotropins. We were able to predict the ovarian response and pregnancy results of patients undergoing ARTs with the use of this simple procedure.

p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease

Background. Indoxyl sulphate (IS) and p-cresyl sulphate (PCS) are uraemic toxins that have similar protein binding, dialytic clearance and proinflammatory features. However, only a few prospective studies have evaluated possible associations between these two retained solutes and renal disease progression in chronic kidney disease (CKD) patients. Methods. This prospective observational study evaluated independent associations between serum total IS and PCS with renal progression in a selected cohort of patients having different stages of CKD. Baseline PCS and IS were correlated with renal progression [defined as decrements in estimated glomerular filtration rate (eGFR) > 50% from baseline or progression to end-stage renal disease (ESRD)] and death during a follow-up period of 24 months. Results. Of 268 patients, 35 (13.1%) had renal progression and 14 (5.2%) died after a mean follow-up of 21 ± 3 months. Univariate Cox regression analysis followed by multivariate analysis showed that high-serum PCS levels were associated with renal progression and all-cause mortality independent of age, gender, diabetes status, albumin levels, serum IS, serum creatinine, Ca × P product, intact parathyroid hormone, haemoglobin or high-sensitivity C-reactive protein level. Serum IS was only associated with renal progression; however, the predictive power of serum IS was weakened when serum PCS was also present in the analytical model. Conclusions. In addition to traditional and uraemia-related risk factors such as renal function, serum IS and PCS levels may help in predicting the risk of renal progression in patients having different stages of CKD.

Multidisciplinary predialysis education decreases the incidence of dialysis and reduces mortality—a controlled cohort study based on the NKF/DOQI guidelines

BACKGROUND Observational studies have demonstrated that multidisciplinary predialysis education (MPE) improves the post-dialysis outcomes of chronic kidney disease (CKD) patients. However, the beneficial effect of MPE remains unclear in prospective controlled studies. METHODS All CKD patients who visited the outpatient nephrology clinics at two centres of the Chang Gung Memorial Hospital in 2006-07 were enrolled. The incidence of dialysis and mortality were compared between MPE recipients and non-recipients. The content of the MPE was standardized in accordance with the NKF/DOQI guidelines. Prognostic factors for progression to end-stage renal disease (ESRD) and all-cause mortality were analysed by using the Cox proportional hazards model. RESULTS Of 573 patients, 287 received MPE. Dialysis was initiated in 13.9% and 43% of the patients in the MPE and non-MPE groups, respectively (P < 0.001). The mean follow-up period was 11.7 +/- 0.9 months. The overall mortality was 1.7% and 10.1% in the MPE and non-MPE groups, respectively (P < 0.001). Cox regression analysis revealed that diabetes, estimated glomerular filtration rate (eGFR), high-sensitive C-reactive protein (hs-CRP) and MPE assignment were significant independent predictors for progression to ESRD. Independent prognostic factors for mortality included age, diabetes, eGFR, hs-CRP and MPE assignment. CONCLUSIONS MPE based on the NKF/DOQI guidelines may decrease the incidence of dialysis and reduce mortality in late-stage CKD patients.

Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy

Aim: The mechanism of pulmonary oedema, a life‐threatening manifestation of enterovirus 71 (EV71) encephalitis, is unclear. Our aim was to assess the relationship of proinflammatory cytokines to EV71‐related pulmonary oedema. Methods: Proinflammatory responses in 33 EV71 patients with various complications and 21 normal healthy children were measured using an enzyme‐linked immunosorbent assay. Results: EV71 patients with both encephalitis and pulmonary oedema were found to have much higher levels of blood interleukin‐6 (IL‐6) (947 ± 1239 vs 4.9 ± 3.1 pg/ml, p= 0.0003), tumour necrosis factor‐α (TNF‐α) (22.4 ± 29.5 vs 5.3 ± 1.0 pg/ml, p= 0.0035), interleukin 1β (IL‐1β) (48.4 ± 85.2 vs 4.9 ± 10.1 pg/ml, p= 0.01), white blood cell count (28.3 ± 7.6 vs 15.5 ± 6.8 109/L, p± 0.0001) and blood glucose (501 ± 186 vs 165 ± 117 mg/dL, p= 0.0009) than patients with EV71 encephalitis alone. In fact, the cytokine levels in patients with encephalitis only or in those without complications were not significantly different from the levels found in normal children. The sensitivity, specificity, positive and negative predictive values of IL‐6 < 70 pg/ml for EV71 encephalitis with pulmonary oedema were all 100%.

Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients—a prospective cohort study

BACKGROUND The mortality rate of elderly hemodialysis (HD) patients is high. Serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) are associated with cardiovascular (CV) disease and mortality in renal patients. The association between such biomarkers and mortality in elderly HD patients has a high clinical value but remains unclear. METHODS This prospective cohort study investigated the association of serum IS and PCS with all-cause and CV mortality in elderly HD patients. Multivariate Cox regression analysis was used to estimate the risk of all-cause and CV mortality in this prospective cohort. RESULTS Of 112 patients, 45 deaths (18 CV deaths) were identified after a mean follow-up of 33.2 months. The cumulative and CV survival of patients with lower free PCS was significantly better than high free PCS patients. In multivariate Cox regression analysis, serum free PCS was associated with all-cause and CV mortality after various adjustments, including age, gender and diabetes status (Model 1), albumin (Model 2), Ca × P product and intact parathyroid hormone (Model 3), hemoglobin and high-sensitivity C-reactive protein (Model 4) and hierarchically selected covariates (age, diabetes status and albumin, Model 5). CONCLUSION Serum free PCS levels may help in predicting risk of all-cause and CV mortality in elderly HD patients beyond traditional and uremia related risk factors.

Neonatal enterovirus infections: emphasis on risk factors of severe and fatal infections.

Objectives. Neonatal enterovirus infections have diverse manifestations, from asymptomatic to fatal. An understanding of the risk factors associated with severe cases might help to reduce enterovirus-related morbidity and mortality. Methods. From July 1989 through June 1998, neonates with virus culture-confirmed nonpolio enterovirus infection at Chang Gung Children’s Hospital were enrolled in the study and divided into three groups: nonspecific febrile illness; aseptic meningitis; and hepatic necrosis with coagulopathy (HNC). Demographic factors, clinical manifestations, laboratory data and outcome were analyzed to reveal factors associated with clinical severity and fatality. Results. There were 146 cases including 43 neonates with nonspecific febrile illness, 61 with aseptic meningitis and 42 with HNC. By multiple logistic regression analysis, the most significant factors associated with HNC were prematurity, maternal history of illness, earlier age of onset (≤7 days), higher white blood cell count (WBC ≥15 000/mm3) and lower hemoglobin (≤10.7 g/dl). In 10 (24%) of 42 cases, HNC was fatal. In comparison with nonfatal cases of HNC, fatal cases had higher WBC, lower hemoglobin, higher bilirubin and higher incidence of concurrent myocarditis. Multivariate analysis showed the most significant factors associated with fatality from HNC to be total bilirubin >14.3 mg/dl (adjusted odds ratio, 29.1; 95% confidence interval, 2.5 to 355.5; P = 0.007) and concurrent myocarditis (adjusted odds ratio, 13.7; 95% confidence interval, 1.1 to 177.2; P = 0.04). Intravenous immunoglobulin did not correlate with clinical outcomes in cases with HNC. Conclusions. Prematurity, maternal history of illness, earlier age of onset, higher WBC and lower hemoglobin are significant factors associated with HNC; higher total bilirubin and concurrent myocarditis were most significantly associated with fatality from HNC.

Factors Associated with Nasal Colonization of Methicillin-Resistant Staphylococcus aureus among Healthy Children in Taiwan

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) has been identified as a major cause of community-associated (CA) S. aureus infections in the past decade. The main reservoir in the community for MRSA and the factors contributing to its worldwide spread remain poorly defined. Between July 2005 and June 2008, a total of 6,057 healthy children 2 to 60 months of age were screened for carriage of S. aureus and Streptococcus pneumoniae in Taiwan. The prevalence and epidemiological factors influencing MRSA carriage were determined. MRSA strains were tested for antimicrobial susceptibility and underwent molecular characterization. The overall prevalences of MRSA and S. aureus carriage were 7.8% and 23.2%, respectively. A majority (88%) of MRSA isolates belonged to a common Asian-Pacific CA-MRSA lineage, multilocus sequence type 59, and were resistant to multiple non-beta-lactam antibiotics. The carriage rate of MRSA was higher among subjects 2 to 6 months old (P < 0.0001), residing in northern Taiwan (P = 0.0003), and enrolled later in the study (P < 0.0001). MRSA colonization was associated with the number of children in the family (adjusted odds ratio [aOR], 1.114; 95% confidence interval [CI], 1.002 to 1.240; P = 0.0463) and day care attendance (aOR, 1.530; 95% CI, 1.201 to 1.949; P = 0.0006). Breast feeding (P < 0.0001) and colonization with S. pneumoniae (P = 0.0170) were protective against MRSA colonization. We concluded that epidemic CA-MRSA strains increasingly colonized Taiwanese children between 2005 and 2008. The carriage rate varied significantly across different demographical features. Crowding was an independent environmental risk factor that might accelerate CA-MRSA transmission in the community.

Prevalence of nocturnal enuresis and associated familial factors in primary school children in taiwan.

PURPOSE We investigated the prevalence and associated factors of nocturnal enuresis in children in elementary schools in Taiwan. MATERIALS AND METHODS A cross-sectional study of nocturnal enuresis in Taiwanese school children was performed in 10 primary schools in Tao-Yuan County, Taiwan. Questionnaires on demographic data, familial and physical conditions were completed by 7,225 children assisted by their parents. RESULTS The overall prevalence of nocturnal enuresis in Taiwanese primary school children was 5.5%. Decreasing age, male gender, family size, birth rank, parental education level and parental raising style were possible familial risk factors for nocturnal enuresis in this study. CONCLUSIONS The study indicates a prevalence of nocturnal enuresis in the Taiwanese population comparable to that in western populations, showing that nocturnal enuresis is an international problem that should be considered seriously. Findings of familial factors associated with nocturnal enuresis provide a clue for future studies of psychosocial factors in different cultural societies and their intervention.

Effect of acupuncture or acupressure on quality of life of patients with chronic obstructive asthma: a pilot study.

OBJECTIVES Acupuncture and acupressure are known to relieve symptoms associated with asthma, but the benefits to patients with chronic obstructive asthma have not been fully evaluated. In this pilot clinical study, acupuncture or acupressure was incorporated into the standard care for adult patients with chronic obstructive asthma to determine their contribution to the improvement of their quality of life and relief of symptoms. DESIGN A prospective, randomized study that involved 8 weeks of treatment at Chang Gung Memorial Hospital (Tao-Yuan, Taiwan) was conducted between March 1997 and September 1998. Forty-one (n = 41) patients with chronic obstructive asthma were enrolled. Patients were randomly assigned to receive acupuncture in addition to standard care (n = 11), acupressure and standard care (n = 17), or standard care alone (n = 13). Twenty (20) acupuncture treatments were administered, and self-administered acupressure was performed daily for 8 weeks. Six-minute walking, the Dyspnea Visual Analogue Scale, the modified Borg scale, St. Georges Respiratory Questionnaire (SGRQ), and the Bronchitis Emphysema Symptom Checklist (BESC) were used at the beginning and end of the 8 weeks of treatment. RESULTS The total SGRQ score of acupuncture subjects showed an average 18.5-fold improvement (95% confidence interval [CI] 1.54-211.48, p = 0.02); the improvement for the acupressure subjects was 6.57-fold (95% C.I. 0.98-44.00, p = 0.05). Additionally, for patients who received acupressure, the irritability domain score determined by the BESC exhibited an 11.8-fold improvement (95% C.I. 0.88-158.64, p = 0.06) after adjustment for covariables. The other variables did not differ from those of the controls. CONCLUSIONS Patients with clinically stable, chronic obstructive asthma experienced clinically significant improvements in quality of life when their standard care was supplemented with acupuncture or acupressure.