Clozapine prescription and quality of life in Chinese patients with schizophrenia treated in primary care.

OBJECTIVE: Clozapine is frequently used to treat schizophrenia in China. Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated the frequency of its use prescribed by primary care physicians. This study described the frequency, demographic and clinical characteristics of clozapine treatment and its impact on insight and quality of life (QOL) of patients with schizophrenia treated in primary care in China. METHOD: A total of 623 patients with schizophrenia treated in 22 primary care services in Guangzhou, China in 2013 formed the study sample. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects and QOL were recorded using a standardized protocol and data collection. RESULTS: The frequency of clozapine prescription was 35.6% with a mean daily dose of 127.7±88.2 mg. There were no significant differences between the patients with and without clozapine in either of the QOL domains after controlling the confounding factors. Multiple logistic regression analyses revealed that patients on clozapine had younger age of onset, more hospitalizations, more severe extrapyramidal side effects, but better insight and fewer prescriptions of first generation antipsychotics. CONCLUSIONS: Clozapine use was found to be common and associated with better insight in patients with schizophrenia treated in primary care in China. Further examination of the rationale and appropriateness of clozapine in primary care in China is warranted.

Systematic review with network meta-analysis: the comparative effectiveness and safety of interventions in patients with overt hepatic encephalopathy.

BACKGROUND: Interventional treatment for overt hepatic encephalopathy (OHE), includes non-absorbable disaccharides, neomycin, rifaximin, L-ornithine-L-aspartate and branched chain amino acids (BCAA). However, the optimum regimen remains inconclusive. AIM: To compare interventions in terms of patients' adverse events and major clinical outcomes. METHODS: Literature search of PubMed, Embase, Scopus, and Cochrane Library studies published up to July 31 2014. RCTs of above interventions in OHE patients were included. Network meta-analysis combined direct and indirect evidence to estimate odds ratios (ORs) and mean difference (MD) between treatments and the probabilities of ranking for treatment based on clinical outcomes. RESULTS: Twenty eligible RCTs were included. When compared with observation, only L-ornithine-L-aspartate (OR 3.71, P < 0.001) and BCAA (OR 3.37, P < 0.001) improved clinical efficacy significantly. However, when L-ornithine-L-aspartate was compared with BCAA, non-absorbable disaccharides and neomycin, there was a trend suggesting that L-ornithine-L-aspartate may be the most effective intervention with respect to clinical improvement (OR 1.10), rifaximin (OR 1.31), non-absorbable disaccharides (OR 2.75), neomycin (OR 2.22). In addition, L-ornithine-L-aspartate (MD -20.18, 95% CI -40.12 to -0.27) provided a significant reduction in blood ammonia concentration compared with observation. Neomycin appeared to be associated with more adverse events in comparison with non-absorbable disaccharides (OR 10.15), rifaximin (OR 17.31), L-ornithine-L-aspartate (OR 3.16) or BCAA (OR 7.69). CONCLUSIONS: L-ornithine-L-aspartate treatment may show a trend in superiority for clinical efficacy among standard interventions for OHE. Rifaximin shows the greatest reduction in blood ammonia concentration, and treatment with neomycin demonstrates a higher probability in causing adverse effects among the five compared interventions.

Systematic review with network meta-analysis: adjuvant therapy for resected biliary tract cancer.

BACKGROUND: Major adjuvant therapies for biliary tract cancer (BTC) include fluorouracil, gemcitabine and chemoradiation (CRT), but the optimum regimen remains inconclusive. AIM: To compare these therapies in terms of patient survival rates after resection and toxic effects. METHODS: We searched PubMed for controlled trials comparing the above three therapies with each other or observation alone until 31 January 2014. We estimated the hazard ratios (HRs) for death and odds ratios (ORs) for toxic effects among different therapies. Subgroup analyses based on positive lymph node or resection margin were also performed. RESULTS: Twelve eligible articles were included. Gemcitabine improved 5-year survival (HR 2.12, 95% CI, confidence interval 1.23-4.02, P = 0.01), whereas fluorouracil (HR 1.61, 95% CI 0.74-3.67) and CRT (HR 1.55, 95% CI 0.82-3.32) provided a poorer survival outcome compared with gemcitabine after 1 year. Similarly, for 5-year survival rates, although differing, CRT did not provide a significant improvement in survival (HR 0.46, 95% CI 0.20-0.97) compared with gemcitabine. Fluorouracil did not appear to provide benefit over gemcitabine (HR 1.56, 95% CI 0.77-3.35). CRT was ranked highest for toxic effects including haematological (OR 5.45, 95% CI 0.01-483.85) and nonhaematological (OR 5.77, 95% CI 0.01-3807.40). CONCLUSIONS: Chemotherapy with gemcitabine is the optimum adjuvant treatment with a balanced benefit-toxicity ratio for resected biliary tract cancer. Chemoradiation was more likely to cause toxic effects.

Andrographolide inhibits oral squamous cell carcinogenesis through NF-κB inactivation.

The NF-κB family of transcription factors is essential for promoting cell proliferation and preventing cell apoptosis. We have previously shown that Andrographolide (Andro) isolated from an herbal plant, Andrographis paniculata, covalently modifies reduced cysteine(62) in the oligonucleotide binding pocket of p50 for inhibition of NF-κB activation. Here we report that Andro, but not its inactive structural analog 4H-Andro, potently suppressed squamous cell carcinogenesis induced by 7,12-dimethyl-1,2-benzanthracene (DMBA) in the hamster model of cheek buccal pouch. Compared with 4H-Andro, Andro reduced phosphorylation of p65 (Ser536) and IκBα (Ser32/36) for inhibiting aberrant NF-κB activation, suppressed c-Myc and cyclin D1 expression and attenuated neoplastic cell proliferation, promoted cancerous cell apoptosis, and mitigated tumor-induced angiogenesis. Consistently, Andro retarded growth, decreased proliferation, and promoted apoptosis of Tb cells, a human tongue squamous cell carcinoma cell line, in time- and dose-dependent manners, with concomitant reduction of the expression of NF-κB targeting molecules in vitro. Our results thus demonstrate that NF-κB activation plays important roles in the pathogenesis of chemically induced squamous cell carcinoma. By inhibition of aberrant NF-κB activation, Andro treats chemically induced oral squamous cell carcinogenesis.

Cloning, expression and location of RNase9 in human epididymis.

BACKGROUND: Mammalian spermatozoa become fully motile and fertile during transit through the luminal fluid of the epididymis. At least 200 proteins are present in the epididymal lumen, but the potential roles of these luminal proteins in male fertility are unknown. Investigation of the function of these proteins will elucidate the mechanism of sperm maturation, and also provide new drug targets for male contraception. We cloned RNase9 from a human epididymis cDNA library for characterization and analysis of its functions. FINDINGS: It was predicted that human RNase9 gene was located on chromosome 14q11.2 and encoded a 205 amino acids protein with a signal peptide of 26 amino acids at the N-terminus. The protein had eight conserved cysteine residues characteristic of the RNase A family members and several potential post-translational modification sites.At the transcriptional level, RNase9 was expressed in a wide variety of tissues, and the expression was higher in men than in boys. RNase9 was localized to the post-equatorial region of the sperms' head. Immunofluorescence staining showed that RNase9 protein was present mostly in the epithelium of the epididymal tubule. Recombinant RNase9 had no ribonuclease activity. In addition, RNase9 had no detectable effect on sperm motility and fertilization as demonstrated by blocking spermatozoa with anti-RNase9 polyclonal serum. CONCLUSION: RNase9 is expressed in a wide variety of tissues. It is located on the post-equatorial region of the sperm head and the epithelium of epididymal tubule. Although RNase9 belongs to the RNase A family, it has no ribonuclease activity.

Total body burden arising from a week's repeated dermal exposure to N,N-dimethylformamide.

BACKGROUND: Hazardous chemicals and their metabolites may accumulate in the body following repeated airborne exposures and skin contact. AIMS: To estimate the contribution of skin absorption to total body burden of N,N-dimethylformamide (DMF) across a working week in two groups with similar levels of respiratory exposure but dissimilar skin contact. METHODS: Twenty five workers in a synthetic leather (SL) factory, 20 in a copper laminate circuit board (CLCB) factory, and 20 age and sex matched non-DMF exposed subjects, were recruited. Environmental monitoring of DMF exposure via respiratory and dermal routes, as well as biological monitoring of pre-shift urinary N-methylformamide (U-NMF), were performed for five consecutive working days. RESULTS: Environmental and biological monitoring showed no detectable exposure in controls. The average airborne DMF concentration (geometric mean (GM) 3.98 ppm, geometric standard deviation (GSD) 1.91 ppm), was insignificantly lower for SL workers than for CLCB workers (GM 4.49, GSD 1.84 ppm). Dermal DMF exposure and U-NMF values, however, were significantly higher for SL workers. A significant pattern of linear accumulation was found across a five day work cycle for SL workers but not for CLCB workers. CONCLUSIONS: Dermal exposure to DMF over five consecutive days of occupational exposure can result in the accumulation of a significant DMF body burden. The long term exposure response under both repeated and intermittent conditions of substantial skin exposure is worthy of note.