Lead time bias might exist in observational study for clinical outcomes. This paper summarizes the concept of lead time bias, causes and control of lead time bias by using the studies of influences of screening diagnostic test on cancer patients'survival and highly active antiretroviral therapy on HIV/AIDS patients' survival as examples for the purpose of providing thinking and methods in the control of lead time bias for the accurate evaluation of the effects of interventions, such as test and treatment, on the diseases with multi courses or phases.
Antiretroviral Therapy, Highly Active ; Bias ; HIV Infections/mortality* ; Humans ; Mass Screening ; Outcome Assessment, Health Care

Objective: To understand the survival status and influencing factors for HIV/AIDS patients on highly active anti-retroviral therapy (HAART) in Shandong province. Methods: Both Kaplan-Meier (K-M) method and cumulative incidence function (CIF) were used to calculate the cumulative incidence of AIDS-related death respectively, and Fine-Gray model was used to identify the influencing factors related to survival time. Results: Through K-M method, a higher AIDS-related cumulated death rate than the CIF, was estimated. Among all the HIV/AIDS patients who initiated HAART from 2003 to 2015 in Shandong, 5 593 of them met the inclusion criteria. The cumulative incidence rate for AIDS-related death was 3.08% in 1 year, 4.21% in 3 years, 5.37% in 5 years, and 7.59% in 10 years respectively by CIF. Results from the F-G analysis showed that HIV/AIDS patients who were on HAART, the ones who had college degree or above (HR=0.40, 95%CI: 0.24-0.65) were less likely to die of AIDS-associated diseases. However, HIV/AIDS patients who were on HAART and living in the western areas of Shandong (HR=1.33, 95%CI: 1.01-1.89), diagnosed by medical institutions (HR=1.39, 95%CI: 1.06-1.80), started to receive care ≥1 year after diagnosis (HR=2.02, 95%CI: 1.30-3.15), their CD(4) cell count less than 200 cells/μl (HR=3.41, 95%CI: 2.59-4.59) at the time of diagnosis, with NVP in antiviral treatment (ART) regime (HR=1.36, 95%CI: 1.03-1.88), at Ⅲ/Ⅳ clinical stages (HR=2.61, 95%CI: 1.94-3.53) and CD(4) cell count less than 350 cells/μl (HR=5.48,95%CI: 2.32-12.72) at initiation of HAART ect., were more likely to die of AIDS-associated diseases. Conclusions: With the existence of competing risks, the cumulative incidence rate for AIDS-related death was overestimated by K-M, suggesting that competing risk models should be used in the survival analysis. Measures as early diagnoses followed by timely care and early HAART could end up with the reduction of AIDS-related death.
Adult ; Anti-Retroviral Agents/therapeutic use* ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; China/epidemiology* ; Female ; HIV ; HIV Infections/mortality* ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome

Influenza can be prevented through annual appropriate vaccination against the virus concerned. In China, influenza vaccine is categorized as "Class Ⅱ" infectious diseases which the cost is paid out of the user's pockets. The annual coverage of influenza vaccination had been 2%-3%. The main reasons for the low coverage would include the following factors: lacking awareness on both the disease and vaccine, poor accessibility of vaccination service, and the cost of vaccination. To reduce the health and economic burden associated with influenza, comprehensive policies should be improved, targeting the coverage of seasonal influenza vaccination. These items would include: ① Different financing reimbursement schemes and mechanisms to improve the aspiration on vaccination and on the vaccine coverage in high-risk groups, as young children, elderly, people with underlying medical conditions; ② to ameliorate equality of vaccination services; ③ to improve knowledge of the health care workers (HCWs) and the public on influenza and related vaccines; ④ to improve clinical and preventive medical practice and vaccination among HCWs through revising clinical guidelines, pathway and consensus of experts; ⑤ to provide more convenient, accessible and normative vaccination service system; ⑥ to strengthen research and development as well as marketing on novel influenza vaccines; ⑦ to revise items regarding the contraindication for influenza vaccine on pregnancy women, stated in the Chinese Pharmacopoeia.
Aged ; Awareness ; Child ; China ; Costs and Cost Analysis ; Female ; Health Knowledge, Attitudes, Practice ; Health Personnel ; Health Promotion/methods* ; Humans ; Influenza Vaccines/economics* ; Influenza, Human/prevention & control* ; Male ; Pregnancy ; Vaccination

Objective: This study aimed to understand the herpes simplex virus-2 (HSV-2) infection and related factors among female drug abusers in the women's compulsory drug rehabilitation center of Shandong province and to provide reference for the prevention and control of HSV-2 in these settings. Methods: We screened all of 451 female drug abusers in the women's compulsory drug rehabilitation centers in of Shandong province and conducted a study using both questionnaire investigation and serological tests for HSV-2, HIV and syphilis. We also used EpiData 3.1 software to establish a database and SPSS 20.0 software to conduct the χ(2) test and multivariate logistic regression analysis. Results: A total of 451 female drug abusers were under study. We noticed that the rates for HSV-2 infection, HIV infection and syphilis infection appeared as 72.1% (325/451), 2.2% (10/451) and 33.5% (151/451) respectively. Results from univariate analysis showed that factors as: awareness on AIDS, having temporary sex partner after using the drug, having multiple sex partners after using the drug, providing commercial services or having temporary sex practice before being detained, with syphilis infection etc., were associated with HSV-2 infection. Data from the multivariate analysis showed that the OR (95%CI) value of HSV-2 infection was 2.90 (1.19-7.06) for those who providing commercial service, when comparing to those who did not. Compared to those who did not suffer from syphilis infection, the OR (95%CI) value of HSV-2 infection for those with syphilis infection was 2.75 (1.63-4.63). Conclusions: The rate of HSV-2 infection was high in the women's compulsory drug rehabilitation center of Shandong province. We should enhance measures and promote condom use to prevent from HSV-2 and other sexually transmitted diseases among them.
Drug Users ; Female ; HIV Infections/epidemiology* ; Herpes Genitalis/epidemiology* ; Herpes Simplex/epidemiology* ; Herpesvirus 2, Human/isolation & purification* ; Humans ; Opiate Substitution Treatment ; Prevalence ; Risk Factors ; Serologic Tests/methods* ; Sexual Behavior ; Sexual Partners ; Substance Abuse Treatment Centers ; Substance-Related Disorders/rehabilitation* ; Syphilis/epidemiology*

Objective: To explore the causes of secondary drug resistance among HIV infected persons who were receiving antiretroviral therapy in Shandong province, and provide evidence for the improvement of antiretroviral therapy strategy. Methods: A case-control study was designed with 1∶2 matching on case and control groups. Household and face-to-face interview were conducted in October, 2015. All the study subjects were screened from both the drug resistant database of antiretroviral therapy of Shandong provincial laboratory and national comprehensive HIV/AIDS database in Shandong. The sample size was estimated as 330 cases including 110 drug resistant and 220 non-drug resistant cases. Subjects were people living with HIV/AIDS (PLWHA) aged 15 or older and received antiretroviral therapy for more than 6 months with records of virus load (VL). Subjects who presented VL above 1 000 copies/ml would receive drug resistance testing. Subjects who were confirmed resistant to with secondary drug, were selected as case group, the rest subjects with non-secondary drug resistance would form the control group. EpiData 3.1 software and SPSS 22.0 software were used to establish a database. Related influencing factors were analyzed with non- conditional stepwise logistic regression model. Results: A total of 288 cases were enrolled, including 103 in the case and 185 cases in the control groups, with average age as (37.62±1.06) years and (37.90±0.74) years old, respectively. Most of them were male, married/cohabitant, with education level of junior/senior high school or below and under Han nationality. Results from the multivariate logistic regression model showed that ORs (95%CI) of receiving antiretroviral therapy for 1-3 years, or more than 3 years were equal to 8.80 (3.69-21.00), 3.00 (1.20-7.53), compared with receiving antiretroviral therapy less than one year, respectively. OR (95%CI) of Among the PLWHA that with missing rate above 25.0% on medication, the OR appeared as 15.41(4.59-51.71), compared with not missing medication. OR (95%CI) among those who took the medicine themselves was 0.22 (0.07-0.74). Conclusions: Factors as duration of treatment, missing rate on medication and taking medicine by oneself were of influence on secondary drug resistance. Other factors as duration on antiretroviral therapy longer than 1 year, missing rate above 25.0% on medication, were related to the risk on secondary drug resistance. However, if the medicine was taken by oneself, it served as a protective factor for secondary drug resistance. It is necessary to strengthen the intervention and health education programs related to antiretroviral therapy.
Adult ; Anti-HIV Agents ; Antiretroviral Therapy, Highly Active ; Case-Control Studies ; Drug Resistance ; HIV/isolation & purification* ; HIV Infections/drug therapy* ; Humans ; Infant ; Logistic Models ; Male

Seasonal influenza vaccination is the most effective way to prevent influenza virus infection and its complications. Currently, China has licensed trivalent (IIV3) and quadrivalent inactivated influenza vaccine (IIV4), including split-virus influenza vaccine and subunit vaccine. In most parts of China, influenza vaccine is a category Ⅱ vaccine, which means influenza vaccination is voluntary, and recipients need to pay for it. To strengthen the technical guidance for prevention and control of influenza and the operational research on influenza vaccination in China, the National Immunization Advisory Committee (NIAC), Influenza Vaccine Technical Working Group (TWG), updated the 2014 technical guidelines and compiled the "Technical guidelines for seasonal influenza vaccination in China (2018-2019)" , based on most recent existing scientific evidences. The main updates include: epidemiology and disease burden of influenza, types of influenza vaccines, northern hemisphere influenza vaccination composition for the 2018-2019 season, and, IIV3 and IIV4 vaccines'major immune responses, durability of immunity, immunogenicity, vaccine efficacy, effectiveness, safety, cost-effectiveness and cost-benefit. The recommendations include: Points of Vaccination clinics (PoVs) should provide influenza vaccination to all persons aged 6 months and above who are willing to be vaccinated and do not have contraindications. No preferential recommendation is made for any influenza vaccine product for persons who can accept ≥1 licensed, recommended, and appropriate products. To decrease the risk of severe infections and complications due to influenza virus infection among high risk groups, the recommendations prioritize seasonal influenza vaccination for children aged 6-60 months, adults ≥60 years of age, persons with specific chronic diseases, healthcare workers, the family members and caregivers of infants <6 months of age, and pregnant women or women who plan to pregnant during the influenza season. Children aged 6 months to 8 years old require 2 doses of influenza vaccine administered a minimum of 4 weeks apart during their first season of vaccination for optimal protection. If they were vaccinated in previous influenza season, 1 dose is recommended. People ≥ 9 years old require 1 dose of influenza vaccine. It is recommended that people receive their influenza vaccination by the end of October. Influenza vaccination should be offered as soon as the vaccination is available. Influenza vaccination should continue to be available for those unable to be vaccinated before the end of October during the whole season. Influenza vaccine is also recommended for use in pregnant women during any trimester. These guidelines are intended for CDC members who are working on influenza control and prevention, PoVs members, healthcare workers from the departments of pediatrics, internal medicine, and infectious diseases, and members of maternity and child care institutions at all levels.
Adult ; Child ; Child, Preschool ; China ; Female ; Guidelines as Topic ; Humans ; Infant ; Influenza Vaccines/administration & dosage* ; Influenza, Human/prevention & control* ; Pregnancy ; Seasons ; Vaccination

Objective: To analyze the epidemiological characteristics, dynamic trend of development and related influencing factors of hepatitis C in Shandong, China, 2007-2016, also to provide epidemiological evidence for prevention and control of HCV. Methods: National surveillance data of hepatitis C from 2007 to 2016 in Shandong was used, with distribution and clustering map of hepatitis C drawn at the county level. Panel Poisson regression was used to explore the influencing factors of hepatitis C at the city level. Results: The incidence of hepatitis C in Shandong increased from 1.49/100 000 in 2007 to 4.72/100 000 in 2016, with the high incidence mainly clustered in the urban regions in Jinan, Zibo, Weihai et al. and surrounding vicinities. Majority of the cases were young adults, with 53.16% (14 711/27 671) of them being farmers. Results from the Multiple panel Poisson regression analysis indicated that factors as: population density (aIRR=1.07, 95%CI: 1.05-1.10), number of hospital per hundred thousand people shared (aIRR=1.16, 95%CI: 1.08-1.24), expenditure of medical fee in rural (aIRR=1.21, 95%CI: 1.08-1.37) and the proportion of the tertiary industry (aIRR=1.08, 95%CI: 1.07-1.09) were all correlated to the incidence of hepatitis C. Conclusions: The incidence of hepatitis C had been increasing rapidly in recent years, in Shandong. Prevention and control of HCV should focus on high risk population. In addition, rural, especially in areas with lower economics provision should be under more attentions, so as to find more concealed cases for early treatment.
Adult ; China/epidemiology* ; Cities ; Hepacivirus ; Hepatitis C/prevention & control* ; Humans ; Incidence ; Population Surveillance ; Young Adult

OBJECTIVE: To investigate the effect of Echinococcus multilocularis infection on Tim3 expression and its co-expression with immune checkpoint molecules 2B4 and LAG3 in spleen natural killer (NK) cells of mice. METHODS: C57BL/6 mice, each weighing (20 ± 2) g, were randomly divided into a high-dose infection group (15 mice), a low-dose infection group (13 mice), and a control group (11 mice). Mice in the high- and low-dose infection groups were inoculated with 2 000 and 50 Echinococcus multilocularis protoscolices via the hepatic portal vein, while animals in the control group was injected with an equivalent amount of physiological saline via the hepatic portal vein. Mouse spleen cells were harvested 12 and 24 weeks post-infection, and Tim3 expression and its co-expression with 2B4 and LAG3 in NK cells were detected using flow cytometry. RESULTS: There were significant differences in the proportions of Tim3 expression (F = 13.559, P < 0.001) and Tim3 and 2B4 co-expression (F = 12.465, P < 0.001) in mouse spleen NK cells among groups 12 weeks post-infection with E. multilocularis, and the proportion of Tim3 expression was significantly higher in mouse spleen NK cells in the low-dose infection group [(23.84 ± 2.28)%] than in the high-dose infection group [(15.72 ± 3.67)%] and the control group [(16.14 ± 3.83)%] (both P values < 0.01), while the proportion of Tim3 and 2B4 co-expression was significantly higher in mouse spleen NK cells in the low-dose infection group [(22.20 ± 2.13)%] than in the high-dose infection group [(14.17 ± 3.81)%] and the control group [(15.20 ± 3.77)%] (both P values < 0.01). There were significant differences in the proportions of Tim3 expression (F = 5.243, P < 0.05) and Tim3 and 2B4 co-expression (F = 4.659, P < 0.05) in mouse spleen NK cells among groups 24 weeks post-infection with E. multilocularis infection, and the proportions of Tim3 expression and Tim3 and 2B4 co-expression were significantly lower in mouse spleen NK cells in the high-dose infection group [(20.55 ± 7.04)% and (20.98 ± 7.12)%] than in the control group [(31.38 ± 3.19)% and (31.25 ± 3.06)%] (both P values < 0.05), and there were no significantly difference between the proportions of Tim3 expression and Tim3 and 2B4 co-expression in splenic NK cells in the low-dose infection group [(26.80 ± 6.47)% and (26.48 ± 6.48)%] and the control group (both P > 0.05). There were no significant differences in the proportions of Tim3 and LAG3 co-expression in mouse spleen NK cells among groups 12 (F = 2.283, P > 0.05) and 24 weeks post-infection (F = 0.375, P > 0.05). In the low-dose infection group, there were no significant differences in the proportions of Tim3 expression or Tim3 and 2B4 co-expression in mouse spleen NK cells 12 (t = -1.137, P > 0.05) or 24 weeks post-infection (t = -1.658, P > 0.05), and the proportion of Tim3 and LAG3 co-expression increased in mouse spleen NK cells 24 weeks post-infection relative to 12 weeks post-infection (t = -5.261, P < 0.01). In the highdose infection group, there was no significant difference in the proportion of Tim3 expression in mouse spleen NK cells 12 and 24 weeks post-infection (t = -1.546, P > 0.05); however, the proportions of Tim3 co-expression with 2B4 and LAG3 increased in mouse splenic NK cells 24 weeks post-infection relative to 12 weeks post-infection (t = -2.425 and -4.745, both P values < 0.05). CONCLUSIONS The Tim3 expression and Tim3 co-expression with LAG3 and 2B4 on spleen NK cells is affected by doses of E. multilocularis infection and disease stages, and present different phenotypes during the course of alveolar echinococcosis. NK cells tend to form an immunosuppressive phenotype with the progression of E. multilocularis infection, which facilitates immune escape and chronic parasitism of E. multilocularis.
Animals ; Mice ; Hepatitis A Virus Cellular Receptor 2/genetics* ; Killer Cells, Natural ; Mice, Inbred C57BL ; Spleen

Background: Wellness programs can be implemented in a university setting and may include varied elements such as physical activity, occupational balance, and vocal health. However, there is limited information that highlights and synthesizes why and how these programs work. Therefore, this study aimed to understand effective programs on physical activity, occupational balance, and vocal health for university constituents in relation to the implementation contexts, mechanisms, and outcomes (CMO). Methodology: Guided by the Health Belief Model in the context of a realist review design, the researchers conducted an iterative search among seven peer-reviewed electronic databases in the health and education fields using a predetermined set of eligibility criteria. Results: The search identified 6564 records, of which programs from 20 records contributed to data synthesis. Nine CMO statements were created, with physical activity programs accounting for most configurations. Key themes identified were tailored and individualized interventions, medium-term incentivization, lifestyle education programs utilizing information and communications technology, interdisciplinary multi-component programs, use of self-monitoring strategies, social support, and shared experiences among employees and students. Analysis of the mechanisms of these effective university programs revealed processes and structures that were consistent with elements of the Health Belief Model. Conclusion Effective university-based PA programs result from a health-supporting culture among staff and students, utilizing self-based, technological, and social approaches that target and address individual and organizational behaviors in physical activity, occupational balance, and vocal health. This realist review provides practical information that may guide the development of university-based programs and policies targeting these areas of wellness.
Exercise ; Work-Life Balance