Modeling methodologies developed for studying pharmacokinetic(PK)/pharmacodynamic(PD) processes confront many challenges related in part to the severe restrictions on the number and type of measurements that are available from laboratory experiments and clinical trials, as well as the variability in the experiments and the uncertainty associated with the processes themselves. Bayesian methods have provided a framework for PK/PD modeling and drug development that can address some of the above-mentioned challenges. This paper presents two illustrations of the application of Bayesian methods: the first involves a population modeling study of the cellular kinetics of the antiretroviral compound Lamivudine in the PBMCs of HIV-1 infected adolescents; the second uses a population mixture modeling approach to identifying hidden subpopulations that can not be identified by available measured covariates.

Introduction Violence is defi ned by the WHO as “the intentional use of physical force or power, threatened or actual, against oneself, another person, or against a group or community, which either results in or has a high likelihood of resulting in injury, death, psychological harm, maldevelopment, or deprivation”. Violence can be divided into many types such as physical, psychological, sexual, neglect and economical etc. Violence against women and child is a manifestation of historically unequal power relations between men and women or child due to patriarchy in many countries of the world. Child maltreatment or violence is one of common public health problems in worldwide and psychologically harm in child’s later life. Objective To detect types, percent and some infl uencing factors of violence against child and adolescent among cases, which were involving into forensic psychiatric evaluation procedures. Materials and Methods We are analyzed all archive documents of NCMH, 2000-2014 by retrospective methodology on based ethical approval of NCMH administration (by ordering 2/189 Oct 28, 2015). Results Total 1067 cases of violence against child and adolescent were registered in 2000-2014 years and 84.7 percent of those (n=904) were sexual violence cases. Gender difference was defi ning among sexual violence cases (girls n=885, p<0.000; boys n=19, p<0.000) with statistically signifi cant. Sexual offender can be act his violence in drunken (OR=2.355; p<0.000; CI 95%; 1.601-3.463) or negative relationship between family members (OR=3.723; p<0.000; CI 95%-2.356-5.883) are more infl uenced to sexual violence against child and adolescent. Conclusion Sexual violence is more registered among child and adolescent maltreatment cases. Children and adolescents are more affected into sexual violence likely to have a negative relationship between the family members or offenders have used alcohol.

Humans ; Diverticulum, Colon ; Fecal Impaction ; Hydrodynamics

A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric (HPLC-ESI-MS/MS) method was developed for the quantification of MHI148-clorgyline amide (NMI-amide), a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMI-amide in mice following intravenous administration. NMI-amide together with the internal standard (IS), MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMI-amide by detecting m/z transition of 491.2–361.9, and 685.3–258.2 for NMI-amide and the IS, respectively. The lower limit of quantification (LLOQ) of the HPLC–MS/MS method for NMI-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2> 0.99 in the concentration range of 0.005–2 μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMI-amide.

In the studies of modern epidemiology, exposure in a short term cannot fully elaborate the mechanism of the development of diseases or health-related events. Thus, lights have been shed on to life course epidemiology, which studies the exposures in early life time and their effects related to the development of chronic diseases. When exploring the mechanism leading from one exposure to an outcome and its effects through other factors, due to the existence of time-variant effects, conventional statistic methods could not meet the needs of etiological analysis in life course epidemiology. This paper summarizes the dynamic path analysis model, including the model structure and significance, and its application in life course epidemiology. Meanwhile, the procedure of data processing and etiology analyzing were introduced. In conclusion, dynamic path analysis is a useful tool which can be used to better elucidate the mechanisms that underlie the etiology of chronic diseases.
Chronic Disease/epidemiology* ; Epidemiologic Studies ; Humans ; Models, Theoretical ; Risk Factors ; Time

Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.
Animals ; Chickens ; China ; Commerce ; Humans ; Influenza A Virus, H7N9 Subtype/pathogenicity* ; Influenza in Birds/virology* ; Influenza, Human/virology* ; Phylogeny ; Poultry/virology* ; Real-Time Polymerase Chain Reaction ; Zoonoses

Objective: To analyze the effect of colorectal cancer screening in the general population in Guangzhou, and provide evidence for the for development of colorectal cancer screening policy and strategy. Methods: The data of colorectal cancer screening in Guangzhou during 2015- 2016 were collected. The participation, the positive rate of fecal occult blood test, the detection rate of colonoscopy and screening effect of colonoscopy were evaluated. Results: A total of 220 834 residents aged 50-74 years received the screening, and the positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively. The detection rates of all colorectal lesions were higher in men than in women (all P<0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer cases were found, accounting for 46.26% of the total cases. The overall screening detection rate of colorectal cancer was 104.15/100 000, higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance (P<0.001), but age group <70 years had higher detection rate, age group ≥70 years had higher incidence rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk, increase the detection rate of colorectal lesions, early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer. The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years. It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.
Adenoma/prevention & control* ; Aged ; China/epidemiology* ; Colonoscopy/statistics & numerical data* ; Colorectal Neoplasms/prevention & control* ; Early Detection of Cancer/methods* ; Female ; Humans ; Immunochemistry ; Male ; Mass Screening/statistics & numerical data* ; Middle Aged ; Occult Blood ; Predictive Value of Tests

Objective: Through analyzing the epidemiological characteristics of hepatitis A and E and the situation of vaccination, to promote the recommendation profile on Hepatitis E vaccination program, in China. Methods: Three phases of time span were divided as 2004-2007, 2008-2011 and 2012-2015, with age groups divided as <20, 20-29, 30-39 and ≥40. Incidence rates in both different phases and age groups were compared. Numbers of Hepatitis A and E vaccines released and used, were described. Results: Between 2004 and 2015, a declining trend in the reported incidence of hepatitis A (t=-12.15, P<0.001), but an increasing trend in hepatitis E (t=6.63, P<0.001) were noticed. The mean number of hepatitis A cases declined from 6 515 to 1 986 between 2004 and 2007 while the number of hepatitis E cases increased from 1 491 to 2 277 between 2012 and 2015. The peaks of hepatitis E appeared persistent annually, in March. The incidence of hepatitis A declined in three regions, with the western region (3.46/100 000) much higher than the eastern (1.13/100 000) or central regions (1.14/100 000) (χ(2)=32 630, P<0.01). The incidence of hepatitis E increased both in the central (1.74/100 000) and western regions (1.58/100 000), but more in the eastern region (2.66/100 000) (χ(2)=6 009, P<0.01). Incidence of hepatitis A declined in all age groups and declined by 84.36% among the 0-19 group. However, the incidence of hepatitis E showed an increasing trend among the ≥20 group. Incidence rates appeared higher in the older age groups. The coverage of hepatitis A vaccine increased from 62.05% to 93.54%, but with a negative association seen between the coverage of Hepatitis A vaccine and the incidence (F=10.69, χ(2)<0.05). Conclusion: The incidence of Hepatitis A declined sharply in China while hepatitis E was still increasing from 2004 to 2015, calling for the expansion on the coverage of Hepatitis E vaccine in the whole population.
Adolescent ; Adult ; Aged ; China/epidemiology* ; Health Care Surveys ; Hepatitis A/epidemiology* ; Hepatitis A Vaccines/administration & dosage* ; Hepatitis E/epidemiology* ; Humans ; Immunization/statistics & numerical data* ; Immunization Programs ; Incidence ; Middle Aged ; Population Surveillance ; Vaccination/statistics & numerical data* ; Young Adult

OBJECTIVETo investigate the impact of novel P2Y(12) receptor inhibitors including prasugrel or ticagrelor on platelet reactivity in patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI), and provide clinical data for novel oral P2Y(12) receptor inhibitors use among Chinese patients.

METHODSBetween October 2011 to February 2014, 174 consecutive patients (135 males; (67.8±11.8) years old) with ACS undergoing PCI in Kiang Wu Hospital, Macau were prospectively enrolled in this study. Oral aspirin and one P2Y(12) receptor inhibitor were administered for 5 days or above after PCI, patients were divided into clopidogrel, prasugrel and ticagrelor groups in accordance with the agent administered. Platelet reactivity of the patients was detected by VerifyNow P2Y(12) reaction unit (PRU); and the high on-treatment platelet reactivity (HPR) and non-HPR were defined as PRU≥208 and PRU<208 respectively. Patients with HPR during clopidogrel therapy were switched either to prasugrel or ticagrelor, or continued the same treatment; and then the platelet reactivity was monitored again.

RESULTSThere were 113 clopidogrel cases (64.9%), 20 prasugrel cases (11.5%) and 41 ticagrelor cases (23.6%). Fifty-seven cases (32.8%) were defined as HPR post P2Y(12) receptor inhibitor use, in which 55 cases (55/113, 48.7%) were treated with clopidogrel. The degree of inhibition of platelet reactivity was significantly different in patients on clopidogrel, prasugrel and ticagrelor therapy, percent inhibition assayed by the VerifyNow P2Y(12) system was 28.2%±23.5%, 61.4%±26.7% and 81.3%±19.8% respectively (P<0.05). Different degree of platelet reactivity was achieved by the 3 P2Y(12) receptor inhibitors at multiple time points. The among-group differences in platelet reactivity became apparent at the early treatment stage (P<0.05). Platelet aggregation decreased significantly in patients switched from clopidogrel to prasugrel or ticagrelor (P<0.05).

CONCLUSIONNovel oral P2Y(12) receptor inhibitors are more effective in inhibiting platelet reactivity in ACS patients, and our results show that novel oral P2Y(12) receptor inhibitors provide a new option for ACS patients with HPR post clopidogrel or high-risk features of ischemic complications, including stent thrombosis and post-PCI ischemic events.

Acute Coronary Syndrome ; Adenosine ; analogs & derivatives ; Aged ; Aspirin ; Blood Platelets ; Female ; Humans ; Male ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; Platelet Function Tests ; Prasugrel Hydrochloride ; Prospective Studies ; Ticlopidine ; analogs & derivatives

Objective: To analyze the prevalence and co-prevalence of cardio metabolic (CM) risk factors in adults in China. Methods: The project data of 2015 Nutritional Status and Health Transition of Chinese Residents were used, and 5 456 adults aged 18-59 years with complete socio-demographic, anthropometric, and blood biochemical data were selected as the study subjects. The definition released by the International Diabetes Federation in 2005 were used to define each CM risk factors, including central obesity, elevated TG, reduced HDL-C, elevated blood pressure and elevated FPG. The co-prevalence of the risk factors was defined as adults having ≥2 risk factors. Multivariable logistic regression analysis was performed to evaluate the relationship between CM risk and socio-demographic factors. Results: About 80.8% of adults had at least 1 risk factor, and 54.0% had co-prevalence of risk factors. Gender, age, education level and living area were significantly associated with the prevalence of major metabolic risk factors. After adjusting for other factors, compared with men, women were more likely to have central obesity and reduced HDL-C, but not more likely to have elevated blood pressure, elevated FPG and elevated TG (P<0.01). Compared with adults aged 18-44 years, adults aged 45-59 years were more likely to have central obesity, elevated blood pressure, elevated FPG and elevated TG (P<0.01). The odds of having central obesity, elevated blood pressure and elevated fasting plasma glucose in the adults in eastern China were significantly higher than those in the central and western China. Conclusions: In 2015, less than 20% of the adults aged 18-59 years in China had no cardio metabolic risk factors, and more than half of them had two or more risk factors. Gender, age and living areas were the major influencing factors. It is necessary to take effective intervention measures targeting adults at high-risk for the early prevention of cardiovascular disease.
Adolescent ; Adult ; Alcohol Drinking/epidemiology* ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Female ; Humans ; Male ; Metabolic Syndrome/ethnology* ; Middle Aged ; Obesity/ethnology* ; Prevalence ; Risk Factors ; Smoking/epidemiology* ; Socioeconomic Factors ; Young Adult