A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine (TCM) products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.
Anaphylaxis ; chemically induced ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; Neural Networks (Computer) ; Product Surveillance, Postmarketing ; Research Design ; Rhabdomyolysis ; chemically induced

OBJECTIVETo evaluate the usefulness of quantitative electroencephalogram (QEEG), flash visual evoked potential (F-VEP) and auditory brainstem responses (ABR) as indicators of general neurological status.

METHODSComparison was conducted on healthy controls (n = 30) and patients with brain concussion (n = 60) within 24 h after traumatic brain injury. Follow-up study of patient group was completed with the same standard paradigm 3 months later. All participants were recorded in multi-modality related potential testing in both early and late concussion at the same clinical setting. Glasgow coma scale, CT scanning, and physical examinations of neuro-psychological function, optic and auditory nervous system were performed before electroencephalogram (EEG) and evoked potential (EEG-EP) testing. Any participants showed abnormal changes of clinical examinations were excluded from the study. Average power of frequency spectrum and power ratios were selected for QEEG testing, and latency and amplitude of F-VEP and ABR were recorded.

RESULTSBetween patients and normal controls, the results indicated: (1) Highly significance (P < 0.01) in average power of α1 and power ratios of θ/α1, θ/α2, α1/α2 of EEG recording; (2) N70-P100 amplitude of F-VEP in significant difference at early brain concussion; and (3) apparent prolongation of I-III inter-peak latency of ABR appeared in some individuals at early stage after concussion. The follow-up study showed that some patients with concussion were also afflicted with characteristic changes of EEG components for both increments of α1 average power and θ/α2 power ratio after 3 months recording.

CONCLUSIONEEG testing has been shown to be more effective and sensitive than evoked potential tests alone on detecting functional state of patients with mild traumatic brain injury (MTBI). Increments of α1 average power and θ/α2 power ratio are the sensitive EEG parameters to determining early concussion and evaluating outcome of post-concussion symptoms (PCS). Follow-up study associated with persistent PCS may be consistent with the postulate of substantial biological, rather than psychological origin. The study suggests that combination of EEG and EP parameters can contribute to the evaluation of brain function as a whole for clinical and forensic applications.

PURPOSE: This study assessed the environmental lead exposure in patients with chronic kidney disease (CKD) and the relationship between lead exposure and renal function indices. METHODS: Seventy-one patients with CKD and 40 control subjects without known renal disease were included. Blood lead was measured by atomic absorption spectrophotometry and tibial lead was measured via 109Cd-based K-shell X-ray fluorescence. Blood urea nitrogen (BUN), serum creatinine, urine creatinine and urine N-acetyl-beta glucosaminidase (NAG) were also measured. Blood lead was corrected with hematocrit (female: 35%, male: 42%) to adjust for differences in anemic status of patients compared with control subjects. RESULTS: The mean level of hematocrit-adjusted blood lead was significantly higher in patients with CKD (4.18+/-1.74 microg/dL) compared with that in control subjects (3.00+/-0.92 microg/dL); the mean tibial lead level tended to be higher in patients with CKD (3.38+/-9.93 microg/g) than that in control subjects (1.28+/-7.92 microg/g), but no statistical significance was observed. In a multivariate regression analysis after adjusting for gender, age, and drinking and smoking status, adjusted blood lead was a significant predictor of increases in BUN and serum creatinine, but not of the level of urine NAG or creatinine. In contrast, no significant association between tibial lead and renal indices was observed in the multivariate regression analysis. CONCLUSION: These results suggest that environmental lead exposure may compromise renal function.
Blood Urea Nitrogen ; Creatinine ; Drinking ; Fluorescence ; Hematocrit ; Hexosaminidases ; Humans ; Renal Insufficiency, Chronic ; Smoke ; Smoking ; Spectrophotometry, Atomic

Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.
Dendritic Cells/immunology ; Female ; Genetic Vectors ; Humans ; *Immunotherapy ; Papillomavirus Infections/*complications/therapy ; Papillomavirus Vaccines/therapeutic use ; *Translational Medical Research ; Uterine Cervical Neoplasms/*therapy ; Vaccines, DNA/therapeutic use ; Vaccines, Subunit/therapeutic use

Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL).Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL),consolidation after systemic therapy,salvage treatment,or palliation.The wide range of presentations of ENL,involving any organ in the body and the spectrum of histological sub-types,poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies.This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians.Thus far there is a lack of guidelines for the use of RT in the management of ENL.This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL,and to address the technical challenges of simulation,volume definition and treatment planning for the most frequently involved organs.Specifically,detailed recommendations for RT volumes are provided.We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL.We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU),as has been widely adopted by the field of radiation oncology for solid tumors.Organ-specific recommendations take into account histological subtype,anatomy,the treatment intent,and other treatment modalities that may be have been used before RT.

INTRODUCTION: We investigated the awareness of palliative care (PC) services in advanced cancer patients and their family caregivers and whether negative perceptions was a possible barrier to PC utilisation in Singapore. MATERIALS AND METHODS: Patients with stage 4 solid cancer and their caregivers were interviewed between July 2016 and March 2018 at outpatient clinics located in the medical oncology departments of 2 major public hospitals in Singapore. Patients and caregivers were asked whether they were aware of PC services, how they first learned about them, who first recommended PC to the patient, whether the patient had received PC, and reasons for not receiving PC. RESULTS: Awareness of PC was lower in patients compared to caregivers (43% vs 53%; <0.01). The odds of being aware in patients was higher if they had higher education (odds ratio [OR] = 2.927; <0.001) and higher income (OR = 1.798; = 0.005). Compared to patients, more caregivers reported that a healthcare provider recommended PC to the patient (10% vs 20%; <0.012). Furthermore, 7% of patients and 15% of caregivers reported that the patient received PC ( = 0.031). The most common reasons for not receiving PC reported by patients and caregivers (respectively) were that the patient was still receiving treatment (68% and 78%), it is not time for PC (76% and 59%) and PC would not be of help (18% and 19%). CONCLUSION Less than half of patients indicated an awareness of PC. Our findings suggest that efforts should be made to increase awareness of PC and promote its acceptance in cancer patients and their family caregivers in Singapore.

Proteins of the complement system are known to interact with many charged substances. We recently characterized binding of C1q and factor H to immobilized and liposomal anionic phospholipids. Factor H inhibited C1q binding to anionic phospholipids, suggesting a role for factor H in regulating activation of the complement classical pathway by anionic phospholipids. To extend this finding, we examined interactions of C1q and factor H with lipid A, a well-characterized activator of the classical pathway. We report that C1q and factor H both bind to immobilized lipid A, lipid A liposomes and intact Escherichia coli TG1. Factor H competes with C1q for binding to these targets. Furthermore, increasing the factor H: C1q molar ratio in serum diminished C4b fixation, indicating that factor H diminishes classical pathway activation. The recombinant forms of the Cterminal, globular heads of C1q A, B and C chains bound to lipid A and E. coli in a manner qualitatively similar to native C1q, confirming that C1q interacts with these targets via its globular head region. These observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain targets. This is distinct from its role as an alternative pathway down-regulator. We suggest that under physiological conditions, factor H may serve as a downregulator of bacterially-driven inflammatory responses, thereby fine-tuning and balancing the inflammatory response in infections with Gram-negative bacteria.
Binding, Competitive ; immunology ; Complement Activation ; immunology ; Complement C1q ; chemistry ; immunology ; metabolism ; Complement C4b ; analysis ; Complement Factor H ; chemistry ; immunology ; metabolism ; Complement Pathway, Classical ; immunology ; Escherichia coli ; immunology ; metabolism ; Humans ; Iodine Radioisotopes ; Isotope Labeling ; Lipid A ; immunology ; metabolism ; Liposomes ; immunology ; metabolism ; Protein Binding ; immunology ; Recombinant Proteins ; chemistry ; immunology ; metabolism ; Substrate Specificity

INTRODUCTIONVancomycin-resistant enterococci (VRE) have emerged as one of the major nosocomial antimicrobial-resistant pathogens globally. In this article, we describe the epidemiology of VRE in Singaporean public hospitals in the 5 years following the major local VRE outbreak in 2005.

MATERIALS AND METHODSA passive laboratory surveillance programme identified non-duplicate VRE isolates from 7 hospitals from 2006 to 2010. Descriptive statistics and time-series analysis was performed on all clinical VRE isolates for each individual hospital as well as for the combined dataset.

RESULTSThere were a total of 418 VRE isolates over 5 years, of which 102 isolates (24.4%) were from clinical cultures. Between 0.4% and 0.7% of all clinical enterococcal isolates were resistant to vancomycin. The overall incidence-density of VRE did not change over time in Singapore despite 2 separate outbreaks in tertiary hospitals in 2009 and 2010. Incidence-density of clinical VRE cases fell in 2 secondary hospitals, while another 2 hospitals experienced no significant VRE infections after 2008.

CONCLUSIONThe prevalence of VRE clinical isolates remains low in Singaporean public sector hospitals. However, the presence of at least 2 outbreaks in separate hospitals over the past 5 years indicates the need for continued vigilance in order to prevent any further increase in VRE prevalence locally.

Anti-Bacterial Agents ; pharmacology ; Cross Infection ; epidemiology ; Enterococcus ; drug effects ; isolation & purification ; Gram-Positive Bacterial Infections ; drug therapy ; Hospitals, Public ; Humans ; Population Surveillance ; Singapore ; epidemiology ; Vancomycin ; therapeutic use ; Vancomycin Resistance ; drug effects

OBJECTIVETo study the effect of Tiantai No. 1 [symbol in text] on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion.

METHODSThirty male Sprague-Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ1-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above three groups were analyzed by using Affymetrix rat whole genome expression profile microarray.

RESULTSMicroarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change >2), and 21 down-regulated genes with significant difference (fold change <0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change >2) and 20 down-regulated genes with significant difference (fold change <0.5). The functions of differentially expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on.

CONCLUSIONTiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.

Alzheimer Disease ; genetics ; pathology ; Animals ; Body Weight ; drug effects ; Computational Biology ; methods ; Drugs, Chinese Herbal ; pharmacology ; Electrophoresis, Agar Gel ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Hippocampus ; drug effects ; metabolism ; pathology ; Male ; Nucleic Acid Denaturation ; Organ Size ; drug effects ; RNA ; isolation & purification ; metabolism ; Rats, Sprague-Dawley

OBJECTIVETo investigate the current smoking regulations and their impacts on the environmental tobacco smoke (ETS) levels inside restaurants and bars in Beijing.

METHODSTelephone survey was used to investigate the smoking regulations. TSI Sidepak AM510 was used to measure the level of fine particles less than 2.5 microns in diameter (PM2.5) in restaurants and bars. Analysis of variance and non-parametric rank tests were used to examine the association between indoor and outdoor PM2.5 levels and (1) smoking regulations; and (2) types of restaurants and bars.

RESULTSOf the 305 restaurants and bars surveyed, 27.9% had complete or partial smoking prohibiting rules. The average indoor PM2.5, level of the 92 restaurants and bars was 253.08 microg/m3 , 102.37% higher than the outdoor level. The average indoor and outdoor PM2.5 levels in the restaurants and bars with smoking ban regulations were 93.10 microg/m3 and 110.33 microg/m3 whole 289.34 microg/m3 and 128.40 microg/m3 in those without, respectively. The average indoor and outdoor PM2.5 levels of bars were 413.46 microg/m3 and 190.62 microg/m3, respectively, while in the western fast-food restaurants, they were 83.86 microg/m3 and 104.77 microg/m3, respectively. The outdoor PM2.5 levels were higher than the indoor levels in different classes of restaurants and bars. Furthermore, there was a significant positive correlation between PM2.5 levels and the number of smokers per cube meters (r = 0.47, P < 0.001).

CONCLUSIONSmoking regulations could effectively reduce the ETS level in restaurants and bars.

Air Pollution, Indoor ; analysis ; legislation & jurisprudence ; China ; Environmental Monitoring ; Particulate Matter ; analysis ; Restaurants ; Smoking ; legislation & jurisprudence ; Tobacco Smoke Pollution ; analysis ; legislation & jurisprudence