[The correlation between burst suppression on electroencephalogram during laparoscopic surgery and emergence delirium in elderly patients].

Objective: To investigate the relationship between intraoperative electroencephalogram burst suppression (BS) and emergence delirium (ED) in elderly patients undergoing elective laparoscopic surgery under total intravenous anesthesia (TIVA). Methods: From October 2017 to September 2019, a total of 358 elderly patients who underwent elective laparoscopic surgery under TIVA at Xiangya Hospital, Central South University, were included. Patients were divided into two groups based on the confusion assessment method for the intensive care unit (CAM-ICU) assessment conducted before leaving the post-anesthesia care unit (PACU): the ED group [n=63, 46 males, 17 females, average age of (70.8±0.6) years] and the non-ED group [n=295, 220 males, 75 females, average age of (69.7±0.2) years]. Preoperative general information, intraoperative conditions, and intraoperative electroencephalogram BS status were collected. A multivariate logistic regression model was employed to identify risk factors associated with ED. Results: In the ED group, the duration of surgery, intraoperative blood loss, the burst suppression ratio (BSR)>10% lasting for more than 1 minute were (224.4±9.6) min, (240.8±33.9) ml, 36.5% (23/63), respectively, which were higher than those of the non-ED group [(204.7±3.6) min, (150.5±9.2) ml, 21.7% (64/295), all P<0.05]. Multivariate logistic regression analysis revealed that a longer duration of education was a protective factor for ED (OR=0.904, 95%CI: 0.833-0.982,P=0.016), whereas increased intraoperative blood loss (OR=1.002, 95%CI: 1.000-1.003, P=0.013) and BSR>10% lasting for more than 1 minute (OR=2.131, 95%CI: 1.004-4.524,P=0.049) were identified as risk factors for ED. Conclusion: In elderly patients undergoing laparoscopic surgery under TIVA, intraoperative electroencephalogram BS may be a risk factor for ED.

[Induction of hepatocellular carcinoma in B6C3 (F1) mice chronicly exposed to trichloroethylene with enhanced acetylation of histone H2AK9ac and SET expression in the liver tissue].

Objective: To establish an animal model of trichloroethylene (TCE) -induced liver cancer following chronic exposure and to understand the changes in SET expression and histone acetylation, potentially serving as a molecular mechanism for TCE-induced hepatocarcinogenesis. Methods: B6C3 mice at 6 weeks were treated with TCE at a series of doses (500, 1000 and 2000 mg/kg) by gastric gavage, with corn oil used as the negative control and carbon tetrachloride (CCl(4)) as the positive control. The serum and liver were sampled for the determination of biochemical indexes and pathological examination after 56 weeks of chemical exposure. Western blot was used to determine the levels of SET, H2AK9ac and HDAC1 expression. Results: The overall survival rate of the mice in various groups was 90.4% (141/156) , with no statistical difference between groups (P>0.05) . Compared with the negative control, the organ coefficient for the liver in the high dose TCE group and the positive control group were significantly increased (P<0.05) . The levels of ALT, AST, LDH and BUN in the all the three TCE groups and the positive control were significantly higher than those in the negative control (P<0.01) . CREA levels in the 1000 and 2000 mg/kg TCE groups were significantly higher than those in the negative control (P<0.05) . Statistical increases in the incidence of hepatocellular carcinoma and the activities of ALT and AST in various doses of TCE-exposed mice as compared with the control were observed (P<0.01) , in a dose-dependent manner. In the 1000 and 2000 mg/kg of TCE treated mice, levels of SET and H2AK9ac were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , Compared to the tissue adjacent to liver cancer, in the 1000 and 2000 mg/kg TCE groups, the levels of SET were increased (P<0.05) , while HDAC1 was decreased (P<0.05) , and H2AK9ac increased in the 2000 mg/kg group. Conclusion: The hepatocellular carcinoma mouse model induced by chronic exposure to trichloroethylene was successfully established, with enhanced SET protein expression and H2AK9ac in the hepatic tissue.

A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression.

BACKGROUND AND PURPOSE: The identification of reliable diagnostic and prognostic biomarkers for Parkinson's disease (PD) is urgently needed. Here, we explored the potential use of α-synuclein (α-syn) in plasma neuronal exosomes as a biomarker for early PD diagnosis and disease progression. METHODS: This study included both cross-sectional and longitudinal designs. The subjects included 36 patients with early-stage PD, 17 patients with advanced PD, 20 patients with idiopathic rapid eye movement sleep behavior disorder and 21 healthy controls (HCs). α-syn levels were measured by electrochemiluminescence immunoassay. A subgroup of patients with early-stage PD (n = 18) participated in a follow-up examination with repeated blood collection and clinical assessments after an average of 22 months. RESULTS: The α-syn levels in plasma neuronal exosomes were significantly higher in patients with early-stage PD compared with HCs (P = 0.007). Differences in α-syn levels between patients with idiopathic rapid eye movement sleep behavior disorder and HCs did not reach statistical significance (P = 0.08). In addition, Spearman correlation analysis revealed that neuronal exosomal α-syn concentrations were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale III/(I + II + III) scores, Non-Motor Symptom Questionnaire scores and Sniffin' Sticks 16-item test scores of patients with PD (P < 0.05). After a mean follow-up of 22 months in patients with early-stage PD, a Cox regression analysis adjusted for age and gender showed that longitudinally increased α-syn rather than baseline α-syn levels were associated with higher risk for motor symptom progression in PD (P = 0.039). CONCLUSIONS: Our results suggested that α-syn in plasma neuronal exosomes may serve as a biomarker to aid early diagnosis of PD and also as a prognostic marker for PD progression.

[Analysis of the potential role of SET in chromium-induced malignant transformation cells based on quantitative proteomics].

Objective: To investigate alteration of proteins profile in malignant transformation bronchial epithelial cells(16HBE-T) induced by hexavalent chromium[(Cr(VI))] and analyze the expression level of SET protein, then to provide some new insights for the carcinogenesis mechanism of Cr(VI). Methods: Total protein was extracted from 16HBE cells and was alkylated and desalinated before digested into peptides. The products were labeled with Tandem Mass Tag (TMT) and identified using LC-ESI-MS/MS. Results: A total of 3 517 proteins were found, expression differences greater than 1.5 or less 0.67 times were to found have 185 and 201 proteins, respectively. Gene enrichment analysis revealed that differential proteins were mainly involved in autophagy, DNA damage repair, RNA processing and other biological processes. Western blot results showed the expression level of SET was significantly increased while downregulated in histone H3K18/27 acetylation and p53 protein. Conclusion: Proteins involved in multiple biological processes altered in 16HBE-T cells and regulation mode of SET inhibiting histone H3K18/27 acetylation regulating transcriptional activity of p53 may paly an important role in Cr(VI)-association carcinogenesis.

[Studies on the DNA damage in the transformed bronchial epithelial cells induced by hexavalent chromium].

Objective: To investigate DNA damage in the transformed human bronchial epithelial cells (16HBE) induced by hexavalent chromium (Cr(6+)) and further elucidate the potential carcinogenesis mechanism of Cr(6+). Methods: 16HBE were treated with different concentration of Cr(6+ ()0, 0.625, 1.25, 2.5 µmol/L) for 15 weeks. The malignant degrees of transformed cells were identified by the assays for anchorage-independent growth and tumorigenicity. According to the single cell gel electrophoresis (SCGE) assay, the DNA damage rate was calculated. The expression level of 53BP1 was determined by Western blot. Results: Chromium-treated cells could form colonies in soft agar and tumors in nude mice. Compared with the control group, colony formation efficiency of 1.25µmol/L and 2.5 µmol/L Cr(6+)-treated cells in soft agar showed significant increases (p<0.05) . The 2.5 µmol/L Cr(6+)-treated cells also formed tumors subcutaneously in nude mice. Cr(6+) could cause different degree of DNA damage to 16HBE cells in a dose-dependent manner. In addition, Western blot analyses showed that 53BP1 was aberrantly down-regulated at 2.5 µmol/L dose and has no significant changes at 0.625 µmol/L and 1.25 µmol/L dose under the treatment of Cr(6+). Conclusion: The declined expression of 53BP1 may mediate Cr(6+)-induced DNA damage and further involved in the cell malignant transformation.

Numerical investigation of airflow, heat transfer and particle deposition for oral breathing in a realistic human upper airway model.

Inhalation injury from exposure to fire smoke is one of the causes of burn-related death. In this study, a realistic three-dimensional human upper airway model was built from magnetic resonance imaging (MRI) scanned images, including the nasal, oral, pharynx, larynx, trachea and part of the first generation of the tracheobronchial tree, as well as a tissue region from the pharynx to the upper bronchi. The Transition Shear Stress Transport (SST-transition) turbulence model, Pennes bioheat transfer equation, convective boundary conditions and a Lagrangian frame were applied and verified with experimental measurements to simulate the airflow fields, temperature distributions and particle deposition in the human airway model. The effects of flow rate, inhalation temperature and particle diameter were studied. It showed that the oral cavity is more likely to be affected by the inlet air conditions. The mucosa in the oral, pharynx and larynx are more likely to cause the thermal injury. The inspiration flow rate significantly influences the airflow fields, temperature distributions and particle deposition fraction interior of the human upper airway model, especially in the pharynx-larynx region. The rising flow rate, inhalation air temperature and particle diameter all contribute to boosting the total deposition fraction in the model. The heated particles with a higher temperature are more likely to be deposited in the oral cavity and the influence of the inlet temperature has a minor influence in the case of a bigger particle diameter.

[Diagnostic value of combining serum soluble ST2 and interleukin-33 for heart failure patients with preserved left ventricular ejection fraction].

Objective: Diagnostic efficacy of serum markers is low for heart failure patients with preserved left ventricular ejection fraction (HF-pEF) as compared to heart failure patients with reduced left ventricular ejection fraction.We sought to explore the diagnostic value of serum levels of soluble ST2 (sST2) combined with interleukin-33 (IL-33) for the diagnosis of HF-pEF in this study. Methods: A total of 376 patients with HF-pEF (HF group), 376 matched-control patients without heart failure who shared similar clinical characteristics (non-HF group) were included in the study.Another 500 healthy individuals were recruited for assessing the normal ranges of IL-33 and sST2.Serum levels of NT-proBNP were measured by chemi-luminescence assay, while IL-33 and sST2 were measured by enzyme linked immunosorbent assay. Results: Serum levels of IL-33 and sST2 were not normally distributed in healthy population.Serum concentrations of IL-33 and sST2 were significantly higher in HF-pEF patients than in patients in non-HF group (median, IL-33: 0.437 µg/L vs. 0.127 µg/L, P<0.01; sST: 0.118 µg/L vs. 0.067 µg/L, P<0.01). The area under receiver operating characteristic curve (AUC) of sST2 for detecting HF-pEF was 0.763 (95%CI 0.729-0.795, P<0.01), with 71.01% sensitivity and 66.75% specificity, the AUC was 0.884 (95%CI 0.859-0.908, P<0.01), with 80.05% sensitivity and 81.91% specificity in patients with serum IL-33 higher than 0.117 µg/L (median level of serum IL-33 in healthy individuals, n=306). The AUC of NT-proBNP for detecting HF-pEF was 0.83, with 74.73% sensitivity and 84.57% specificity.The AUC of sST2 for detecting HF-pEF was significantly higher than NT-proBNP in population with high serum IL-33 (AUC: 0.88 vs. 0.83, P<0.01). Conclusion: Serum sST2 could serve as a satisfactory biomarker for HF-pEF diagnosis, especially for patients with high serum IL-33 concentrations.

Association of PELI1 polymorphisms in systemic lupus erythematosus susceptibility in a Chinese population.

OBJECTIVE: Studies in animal models have indicated that Pellino 1 is involved in inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE). The current study was designed to determine whether PELI1 confers genetic susceptibility to SLE in humans, as assessed in a Chinese Han population. METHODS: Blood samples were drawn from patients diagnosed with SLE and healthy volunteers. Three single nucleotide polymorphism (SNP) loci with a minor allele frequency of at least 0.05 were chosen to evaluate the correlation between PELI1 genotype and the incidence of SLE. RESULTS: There was a significant difference in the frequency distribution of the rs329497 allele between the SLE patients and the healthy controls (A vs. G; Bonferroni corrected p = 0.036, odds ratio = 0.75, 95% confidence interval = 0.60-0.94). No differences in the genotype and allele frequencies of other SNP loci were observed between the two groups. Furthermore, the alleles and genotypes of the three SNPs were not associated with lupus nephritis. CONCLUSION: In the Chinese Han population, PELI1 SNPs may be associated with SLE susceptibility.

Cross-cultural measurement equivalence of the EQ-5D-5L items for English-speaking Asians in Singapore.

PURPOSE: To investigate how the response labels of the 5-level EQ-5D (EQ-5D-5L) items are interpreted and used by English-speaking Chinese and non-Chinese Singaporeans, as a means to assessing whether those items are cross-culturally equivalent health-status measures in this Asian population. METHODS: In face-to-face interviews, Chinese, Malay and Indian visitors to a primary care institution in Singapore were asked to rate the relative severity conveyed by EQ-5D-5L response labels, each containing the keyword of 'no(t),' 'slight(ly),' 'moderate(ly),' 'severe(ly),' or 'unable'/'extreme(ly),' using a 0-100 numerical rating scale. Participants were also asked to describe 25 hypothetical health states using the EQ-5D-5L response labels. Differences between Chinese and Malay/Indian participants in label interpretation and selection were examined using multivariate regression analysis to adjust for participant characteristics. RESULTS: The differences in adjusted mean severity scores for individual EQ-5D-5L labels between Chinese (n = 148) and non-Chinese (Malay: n = 53; Indian: n = 56) participants ranged from 0.0 to 9.0. The relative severity of the labels to the participants supported the ordinality of the EQ-5D-5L response labels and was similar across ethnic groups. Chinese and non-Chinese participants selected similar response labels to describe each hypothetical health state, with the adjusted odds ratios of selecting any type of the five response labels for non-Chinese versus Chinese participants ranging from 0.92 to 1.15 (p > 0.05 for all). CONCLUSIONS: The EQ-5D-5L items are likely to generate equivalent health outcomes between English-speaking Chinese and non-Chinese Singaporeans.

Health-related quality of life of Asian patients with end-stage renal disease (ESRD) in Singapore.

BACKGROUND: This study aimed to identify factors associated with the health-related quality of life (HRQOL) of multiethnic Asian end-stage renal disease (ESRD) patients treated with dialysis. The role of dialysis modality was also explored. METHODS: Data used in this study were from two cross-sectional surveys of Singaporean ESRD patients on haemodialysis (HD) or peritoneal dialysis (PD). In both surveys, participants were assessed using the kidney disease quality of life (KDQOL) instrument and questions assessing socio-demographic characteristics. Clinical data including co-morbidity (measured by Charlson comorbidity index [CCI]), albumin level, haemoglobin level, and dialysis-related variables (e.g. dialysis vintage and dialysis adequacy) were retrieved from medical records. The 36-item KDQOL (KDQOL-36) was used to generate three summary scores (physical component summary [PCS], mental component summary [MCS] and kidney disease component summary [KDCS]) and two health utility scores (Short Form 6-dimension [SF-6D] and EuroQol 5-dimension [EQ-5D]). Linear regression analysis was performed to examine the association of factors with each of the HRQOL scale scores. RESULTS: Five hundred and two patients were included in the study (mean age 57.1 years; male 52.4 %; HD 236, PD 266). Mean [standard deviation (SD)] PCS, MCS and KDCS scores were 37.9 (9.7), 46.4 (10.8) and 57.6 (18.1), respectively. Mean (SD) health utility score was 0.66 (0.12) for SF-6D and 0.60 (0.21) for EQ-5D. In multivariate regression analysis, factors found to be significantly associated with better HRQOL included: young (<45 years) or old age (>60 years), low CCI (<5), high albumin (≥37 g/l) and high haemoglobin (≥11 g/dl) with PCS; long dialysis vintage (≥3.5 years) with MCS; old age, Malay ethnicity and PD modality with KDCS; low CCI, high albumin and high haemoglobin with EQ-5D and high albumin with SF-6D. CONCLUSIONS: Clinical characteristics are better predictors of HRQOL in ESRD patients than socio-demographics in Singapore. Dialysis modality has no impact on the health utility of those patients.

Immunological changes after ASIT in AD allergen-specific immunotherapy and their potential correlation with clinical response in patients with atopic dermatitis patients sensitized to house dust mite.

BACKGROUND: Allergen-specific immunotherapy (ASIT) is the main treatment for inducing long-term immunological and clinical tolerance in patients with IgE-mediated allergic diseases. Recent open-label and controlled studies on the efficacy of ASIT in patients with atopic dermatitis (AD) have provided promising results. However, data about possible relationship between the improvement of clinical symptoms and changes of serum cytokines are limited. METHODS: Seventy-nine patients with moderate to severe AD sensitized to house dust mite (HDM) were enrolled. Fifty-eight patients were treated with ASIT and 11 controls received only symptomatic treatment. The disease activity in AD patients was evaluated by using the patient-oriented eczema measure (POEM) system. Serum interleukin (IL)-4, IL-10, interferon (IFN)-γ, transforming growth factor (TGF) ß1, total IgE, HDM-specific IgE (s-IgE) and HDM-specific IgG4 (s-IgG4) were measured before and after 2 years of therapy. RESULTS: The mean patient-oriented eczema measure system (POEM) score of AD patients with ASIT significantly decreased after 2 years of treatment, compared to that in patients without ASIT. After ASIT, the serum levels of IL-10, TGF-ß1, IFN-γ and s-IgG4 increased, while the level of IL-4 decreased. The change in the POEM score was negatively correlated with changes of serum concentration of TGF-ß1, s-IgG4 and IFN-γ. Furthermore, s-IgG4 levels were positively correlated with changes in the IL-10 levels. No correlation between POEM score and serum IL-10 or IL-4 was observed. CONCLUSION: Clinical symptoms and the quality of life of AD with HDM sensitization could be improved after 2 years of ASIT. Changes in serum IL-10, TGF-ß1, s-IgG4 and IFN-γ might be considered as biomarkers to assist clinical evaluation of the therapeutic effects of ASIT in patients with AD.

Prostaglandin A2 enhances cellular insulin sensitivity via a mechanism that involves the orphan nuclear receptor NR4A3.

We have previously reported that members of the NR4A family of orphan nuclear receptors can augment insulin's ability to stimulate glucose transport in adipocytes. In the current study, we endeavored to test for an insulin-sensitizing effect in muscle cells and to identify a potential transactivator. Lentiviral constructs were used to engineer both hyperexpression and shRNA silencing of NR4A3 in C2C12 myocytes. The NR4A3 hyper-expression construct led to a significant increase in glucose transport rates in the presence of maximal insulin while the NR4A3 knock-down exhibited a significant reduction in insulin-stimulated glucose transport rates. Consistently, insulin-mediated AKT phosphorylation was increased by NR4A3 hyperexpression and decreased following shRNA NR4A3 suppression. Then, we examined effects of prostaglandin A2 (PGA2) on insulin action and NR4A3 transactivation. PGA2 augmented insulin-stimulated glucose uptake in C2C12 myocytes and AKT phosphorylation after 12-h treatment, without significant effects on basal transport or basal AKT phosphorylation. More importantly, we demonstrated that PGA2 led to a greater improvement in insulin-stimulated glucose rates in NR4A3 overexpressing C2C12 myocytes, when compared with Lac-Z controls stimulated with insulin and PGA2. Moreover, the sensitizing effect of PGA2 was significantly diminished in NR4A3 knockdown myocytes compared to scramble controls. These results show for the first time that: (i) PGA2 augments insulin action in myocytes as manifested by enhanced stimulation of glucose transport and AKT phosphorylation; and (ii) the insulin sensitizing effect is dependent upon the orphan nuclear receptor NR4A3.

Overuse of paracetamol caffeine aspirin powders affects cerebral glucose metabolism in chronic migraine patients.

BACKGROUND AND PURPOSE: Overuse of analgesic plays a prominent role in migraine chronification. Paracetamol caffeine aspirin (PCA) powders are commonly used in Chinese migraineurs. This study investigated the effects of the specific combination analgesic on cerebral glucose metabolism in chronic migraine (CM). METHODS: 18F-FDG-PET was used to measure regional metabolism in all subjects. Brain metabolisms of CM patients with analgesic overuse (AO-CM; n=10), no analgesic overuse (NAO-CM; n=10), and no regimen (NR-CM; n=10) and 17 age- and gender-matched normal controls (NC) were compared using statistical parametric mapping. Then, all patients underwent brain MRI analysis within 7 days after PET scans, as well as MMSE and MoCA scale for cognitive function tests. RESULTS: Glucose metabolic changes in CM patients taking different dosage of analgesic during headache-free periods and clear distinctions in several brain regions were observed. Patients with AO-CM exhibited significant metabolic reductions in thalamus, as well as increased metabolism in middle temporal gyrus and insula relative to NR-CM and NAO-CM. However, in these regions, no difference was observed in AO-CM except for increased metabolism in the right insula relative to NC group. CONCLUSIONS: Overusing PCA powders affects regional brain glucose metabolism in CM. Increased metabolism in the right insula may be associated with recurrently overusing of PCA powders.

Estimating the lifetime economic burden of Parkinson's disease in Singapore.

BACKGROUND AND PURPOSE: We aimed to estimate the lifetime cost of Parkinson's disease (PD) from the societal perspective. METHODS: A convenience sample of English or Chinese-speaking patients with PD was recruited from a PD and Movement Disorders Centre in Singapore to complete a financial burden questionnaire. Sociodemographic and clinical data were retrieved from hospital databases. Markov cohort model analysis was performed (cycle length, 1-year; duration, death or reached 100 years old). Patients were assumed to progress from one Markov state to the next state or death without skipping states or regressing. All model parameters were based on published local data. RESULTS: In 195 patients with PD (median age: 68.9, male: 51.8%), the simulated lifetime cost of PD was Singapore Dollar (SGD) 60,487 (EUR purchasing power parity 56,253) per patient. Direct medical, non-medical and indirect cost accounted for 18.8%, 12.8% and 68.4% of total lifetime cost, respectively. The top three components of total lifetime cost were productivity losses (67.6%), pharmacotherapy (11.4%) and home care (8.7%). One-way sensitivity analysis and probabilistic sensitivity analyses revealed that estimates were sensitive to cost at H&Y stage 1, 2 and 2.5 and productivity losses. CONCLUSIONS: The lifetime cost of PD is evaluated for the first time. This cost is substantial and comparable to the lifetime cost of intracerebral haemorrhage in at least one study. Our study identified several priority areas for research and policy formulation: reducing productivity losses, reducing cost of pharmacotherapy, avoiding hospitalization and reducing home care cost.

Predicting preference-based SF-6D index scores from the SF-8 health survey.

PURPOSE: To develop and test functions for predicting the preference-based SF-6D index scores from the SF-8 health survey. METHODS: This study was a secondary analysis of data collected in a population health survey in which respondents (n = 7,529) completed both the SF-36 and the SF-8 questionnaires. We examined seven ordinary least-square estimators for their performance in predicting SF-6D scores from the SF-8 at both the individual and the group levels. RESULTS: In general, all functions performed similarly well in predicting SF-6D scores, and the predictions at the group level were better than predictions at the individual level. At the individual level, 42.5-51.5% of prediction errors were smaller than the minimally important difference (MID) of the SF-6D scores, depending on the function specifications, while almost all prediction errors of the tested functions were smaller than the MID of SF-6D at the group level. At both individual and group levels, the tested functions predicted lower than actual scores at the higher end of the SF-6D scale. CONCLUSIONS: Our study developed functions to generate preference-based SF-6D index scores from the SF-8 health survey, the first of its kind. Further research is needed to evaluate the performance and validity of the prediction functions.

Use of maggot debridement therapy for tropical diabetic hand syndrome.

Diabetic patients with infectious hand ulceration, known as tropical diabetic hand syndrome (TDHS), are generally less well recognised than those with foot ulcers. Maggot debridement therapy (MDT) is usually used for the treatment of diabetic foot ulcers and, in these wounds, the remarkable wound cleansing properties can be of considerable value. However, it is less commonly used in TDHS. Here we present a case of TDHS in a 51-year-old man with type II diabetes, hypertension and dilated cardiomyopathy, in which conventional therapy had minimal effect, but significant wound debridement was achieved with MDT. This suggests that MDT may be a cost-effective alternative to conventional treatments for the debridement of TDHS.

[Outcomes at discharge of preterm infants born <34 weeks' gestation].

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.

Economic burden of Parkinson's disease in Singapore.

BACKGROUND: This study was carried out to evaluate the economic burden of Parkinson's disease (PD) and factors independently associated with individual components of total cost in Singapore. METHODS: A consecutive sample of 195 patients with PD (mean age: 68.2, men: 51.8%) attending a tertiary neuroscience clinic were identified and interviewed using standardized questionnaires including a financial burden questionnaire, two Health Related Quality of Life (HRQoL) questionnaires and the Beck Depression Inventory questionnaire. RESULTS: Annual total cost of PD from a societal perspective was SGD11345 (USD10129) per patient, with direct cost accounted for 38.5% and indirect cost 61.5%. The main cost components for direct medical cost, direct non-medical cost, and indirect cost was pharmacotherapy (50.4%), home care (76.1%), and productivity loss (97.9%), respectively. In multiple linear regression analysis, higher education, younger age and longer duration of PD were associated with higher total cost. CONCLUSIONS: Parkinson's disease exerts a considerable burden on patients, health care system and society in Singapore. As productivity loss accounts for a large share of the economic burden imposed by PD, treatments and health care programmes with potential for returning patients to higher productivity are urgently needed.