Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.     

Assessing the Consistency of Traditional Chinese Medicine with Multiple Correlative Active Components

The problem of controlling the quality of raw materials and/or final product of traditional Chinese medicine (TCM) has been studied. Earlier proposed consistency index to assess the consistency of quality of raw materials and/or final product processed or manufactured from different locations or sites has only focused on a single (i.e., the most active) component assuming that the most active component can be quantitatively identified among multiple active components. In this paper, we extend such results to the case of two correlative components. Sampling plans (sample sizes) are obtained for various combinations of study parameters. An example concerning a TCM for treating patients with rheumatoid arthritis is presented to illustrate the use of the proposed method. Some concluding remarks are also provided.     

Toxicity assessment and vitellogenin expression in zebrafish (Danio rerio) embryos and larvae acutely exposed to bisphenol A,endosulfan, heptachlor,methoxychlor and tetrabromobisphenol A

Organochlorine pesticides and brominated flame retardants, such as tetrabromobisphenol A and polybrominated diphenyl ethers, pose an environmental hazard owing to their persistence, low solubility and estrogenic effects, and concerns have been raised regarding their effects on aquatic biota. In the present study, zebrafish embryos and larvae were used as a model to investigate the sublethal and lethal effects of three different organochlorine pesticides, namely methoxychlor, endosulfan and heptachlor, as well as the flame retardant tetrabromobisphenol A, and its precursor compound bisphenol A. Preliminary data for chemical exposure tests were obtained by determining the 96 h median effective concentration EC₅₀ (hatching rate) and 96 h median lethal concentration LC₅₀. Quantitative polymerase chain reaction was used to investigate the gene expression levels of the biomarker vitellogenin (vtg1) after 96 h exposures to 10, 25, 50 and 75% of the 96 h EC₅₀ value for embryos and 96 h LC₅₀ value for larvae. The use of vtg1 mRNA induction in zebrafish embryos and larvae was found to be a sensitive biomarker of exposure to these organic compounds, and was helpful in elucidating their adverse effects and setting water quality guidelines. Copyright © 2012 John Wiley & Sons, Ltd.     

HIV-Induced Cystopathy

The prevalence of voiding dysfunction in patients with HIV has decreased dramatically since the inception of highly active antiretroviral therapy (HAART) and therefore has not been an area that has been widely published. Prior research into this area was at the epidemic’s onset, when there was a large population of patients with opportunistic infections and associated voiding dysfunction. As the HAART patients are living longer and symptom-free lives, there is no current large population from which to draw in order to conduct sound studies. Through a comprehensive review of the literature, we discuss the most common causes of HIV-induced cystopathy to educate the practicing urologist about disease-related causes and to serve as a guide for the diagnosis and management of HIV-associated voiding dysfunction.     

Statistical and regulatory considerations in assessments of interchangeability of biological drug products

When the patent of a brand-name, marketed drug expires, new, generic products are usually offered. Small-molecule generic and originator drug products are expected to be chemically identical. Their pharmaceutical similarity can be typically assessed by simple regulatory criteria such as the expectation that the 90 % confidence interval for the ratio of geometric means of some pharmacokinetic parameters be between 0.80 and 1.25. When such criteria are satisfied, the drug products are generally considered to exhibit therapeutic equivalence. They are then usually interchanged freely within individual patients. Biological drugs are complex proteins, for instance, because of their large size, intricate structure, sensitivity to environmental conditions, difficult manufacturing procedures, and the possibility of immunogenicity. Generic and brand-name biologic products can be expected to show only similarity but not identity in their various features and clinical effects. Consequently, the determination of biosimilarity is also a complicated process which involves assessment of the totality of the evidence for the close similarity of the two products. Moreover, even when biosimilarity has been established, it may not be assumed that the two biosimilar products can be automatically substituted by pharmacists. This generally requires additional, careful considerations. Without declaring interchangeability, a new product could be prescribed, i.e. it is prescribable. However, two products can be automatically substituted only if they are interchangeable. Interchangeability is a statistical term and it means that products can be used in any order in the same patient without considering the treatment history. The concepts of interchangeability and prescribability have been widely discussed in the past but only in relation to small molecule generics. In this paper we apply these concepts to biosimilars and we discuss: definitions of prescribability and interchangeability and their statistical implementation; the relation between bioequivalence and interchangeability for small-molecule drug products; regulatory requirements and expectations of biosimilar products in various jurisdictions; possible statistical approaches to establish the similarity and interchangeability of biologic drug products; definition of other technical terms such as switchability and automatic substitution. The paper will be concluded with a discussion of the anticipated future use of interchangeability of biological drug products.     

A time to be born and a time to die: Exploring the determinants of death anxiety among university students in a western Canadian city

Using data collected from a questionnaire survey of 501 university students in a western Canadian city, this article explores the death anxiety among young adults and the factors influencing their levels of death anxiety. Results demonstrated that respondents displayed a moderate level of death anxiety. Multiple regression analysis further revealed that females, non-Caucasians and those who demonstrated to be less religious, indicated a higher level of loneliness, scored lower on the purpose in life scale, expressed dissatisfaction with their self-image, and reported a higher socio-economic status were found to exhibit a higher level of death anxiety.