Long-term persistent immunogenicity after successful standard and triple-dosed hepatitis B vaccine in hemodialysis patients: A 3-year follow-up study in China

BackgroundAlthough the efficacy of hepatitis B vaccines among hemodialysis patients has been documented, the long-term persistence of immunogenicity in this population remains largely unknown. We explored the long-term persistence of immunogenicity induced by different hepatitis B vaccine regimens in hemodialysis patients.MethodsIn initial study, we conducted a randomized, multicenter, double-blind, parallel-controlled trial among hemodialysis patients in 13 hospitals in Shanxi Province, China. A total of 352 hemodialysis patients were allocated to receive 3-dose 20 μg (IM20 group) and 3-dose 60 μg (IM60 group) recombinant hepatitis B vaccine at months 0, 1, and 6. Vaccine-induced immune responses were measured at month 7. In this study, the responders (anti-HBs ≥ 10 mIU/mL) were followed up at months 18, 24, 30, 36 and 42, respectively. We used the generalized log-rank test and generalized estimating equations (GEE) to analyze the long-term durability of responses and the kinetics of anti-HBs levels, respectively.ResultsA total of 284 patients were involved in the extended follow-up period. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 12 months and 18 months in the IM20 group and IM60 group, respectively (P = 0.291). The long-term persistent immunogenicity induced by 3-dose 60 μg was more satisfactory than that by 3-dose 20 μg hepatitis B vaccine in patients with hemodialysis duration ≥ five years (P = 0.023). The peak anti-HBs levels in 100–1000 mIU/mL or ≥ 1000 mIU/mL were more likely to maintain long-term protective antibody compared to anti-HBs levels in 10–100 mIU/mL (P ＜ 0.05). The kinetic profile was similar between the two groups (P = 0.334).ConclusionHigh-dose 60 μg hepatitis B vaccine could lead a satisfactory long-term durability of immunogenicity among patients with hemodialysis duration of five years or more. Peak anti-HBs level after vaccination was associated with the long-term persistence of immunogenicity.     

Local ancestry at APOE modifies Alzheimer's disease risk in Caribbean Hispanics

IntroductionAlthough the relationship between APOE and Alzheimer's disease (AD) is well established in populations of European descent, the effects of APOE and ancestry on AD risk in diverse populations is not well understood.MethodsLogistic mixed model regression and survival analyses were performed in a sample of 3067 Caribbean Hispanics and 3028 individuals of European descent to assess the effects of APOE genotype, local ancestry, and genome-wide ancestry on AD risk and age at onset.ResultsAmong the Caribbean Hispanics, individuals with African-derived ancestry at APOE had 39% lower odds of AD than individuals with European-derived APOE, after adjusting for APOE genotype, age, and genome-wide ancestry. While APOE E2 and E4 effects on AD risk and age at onset were significant in the Caribbean Hispanics, they were substantially attenuated compared with those in European ancestry individuals.DiscussionThese results suggest that additional genetic variation in the APOE region influences AD risk beyond APOE E2/E3/E4.     

Potential Overtreatment and Undertreatment of Type 2 Diabetes Mellitus in Long-Term Care Facilities: A Systematic Review

ObjectiveTo investigate the prevalence, outcomes, and factors associated with potential glycemic overtreatment and undertreatment of type 2 diabetes mellitus (T2DM) in long-term care facilities (LTCFs).DesignSystematic review.Setting and ParticipantsResidents with T2DM and aged ≥60 years living in LTCFs.MeasuresArticles published between January 2000 and September 2020 were retrieved following a systematic search of MEDLINE, EMBASE, Cochrane Library, CINAHL plus, and gray literature. Inclusion criteria were the reporting of (1) potential overtreatment and undertreatment quantitatively defined (implicitly or explicitly) based on hemoglobin A1c (HbA1c) and/or blood glucose; (2) prevalence, outcomes, and associated factors of potential glycemic overtreatment and undertreatment; and (3) the study involved residents of LTCFs.ResultsFifteen studies were included. Prevalence of potential overtreatment (5%–86%, n = 15 studies) and undertreatment (1.4%–35%, n = 8 studies) varied widely among facilities and geographical locations, and according to definitions used. Prevalence of potential overtreatment was 16%–74% when defined as treatment with a glucose-lowering medication in a resident with ≥1 hypoglycemia risk factor or serious comorbidity, together with a HbA1c <7% (n = 10 studies). Potential undertreatment was commonly defined as residents on glucose-lowering medication having HbA1c >8.5% and the prevalence 1.4%–14.8% (n = 6 studies). No studies prospectively measured resident health outcomes from overtreatment and undertreatment. Potential overtreatment was positively associated with use of oral glucose-lowering medications, dementia diagnosis or dementia severity, and/or need for assistance with activities of daily living (n = 2 studies). Negative association was found between potential overtreatment and use of insulin/combined insulin and oral glucose-lowering medication. No studies reported factors associated with potential undertreatment.Conclusions and ImplicationsThe prevalence of potential glycemic overtreatment and undertreatment varied widely among residents with T2DM depending on the definition(s) used in each study. Longitudinal studies examining associations between glycemic management and health outcomes, and the use of consensus definitions of overtreatment and undertreatment are required to establish findings about actual glycemic overtreatment and undertreatment in LTCFs.     

Inclusion of membrane-anchored LTB or flagellin protein in H5N1 virus-like particles enhances protective responses following intramuscular and oral immunization of mice

We previously demonstrated that intramuscular immunization with virus-like particles (VLPs) composed of the haemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) protected mice from lethal challenge with viruses from other H5 HPAI clades. The inclusion of additional proteins that can serve as immunological adjuvants in VLPs may enhance adaptive immune responses following vaccination, and oral vaccines may represent the safest choice. Here, we report the generation of H5N1 VLPs composed of the viral HA, NA, and M1 proteins and membrane-anchored forms of the Escherichia coli heat-labile enterotoxin B subunit protein (LTB) or the Toll-like receptor 5 ligand flagellin (Flic). Mice intramuscularly or orally immunized with VLPs containing LTB or Flic generated greater humoural and cellular immune responses than those administered H5N1 VLPs without LTB or Flic. Intramuscular immunization with VLPs protected mice from lethal challenge with homologous or heterologous H5N1 viruses irrespective of whether the VLPs additionally included LTB or Flic. In contrast, oral immunization of mice with LTB- or Flic-VLPs conferred substantial protection against lethal challenge with both homologous and heterologous H5N1 influenza viruses, whereas mice immunized orally with VLPs lacking LTB and Flic universally succumbed to infection. Mice immunized orally with LTB- or Flic-VLPs showed 10-fold higher virus-specific IgG titres than mice immunized with H5N1-VLPs lacking LTB or Flic. Collectively, these results indicate that the inclusion of immunostimulatory proteins, such as LTB and Flic, in VLP-based vaccines may represent a promising new approach for the control of current H5N1 HPAI outbreaks by eliciting higher humoural and cellular immune responses and conferring improved cross-clade protection.     

Systematic review of cost-effectiveness studies of human papillomavirus (HPV) vaccination: 9-Valent vaccine,gender-neutral and multiple age cohort vaccination

BackgroundThe success of human papillomavirus (HPV) national immunization program depends on effective strategies in optimizing the uptake of HPV vaccine. Given the increasing number of economic evaluations, this review was conducted to update the economic evidence on HPV vaccination, by focusing on: (i) 9-valent vaccine compared to bi- or quadrivalent vaccine; (ii) gender-neutral vaccination compared to female only vaccination; and (iii) multiple age cohort immunization compared to single age cohort immunization.MethodsSearches were performed until June 2016 using 4 databases: PubMed; Embase; Cochrane Library; and LILACS. The combined WHO, Drummond and CHEERS checklist were used to evaluate the quality of included studies.ResultsThirty-four studies were included in the review and most of them were conducted in high-income countries. The inclusion of adolescent boys in vaccination program was found to be cost-effective if vaccine price and coverage was low. When coverage for female was above 75%, gender-neutral vaccination was less cost-effective than when targeting only girls aged 9–18 years. Current evidence does not show conclusive proof of greater cost-effectiveness of 9-valent vaccine compared to the older HPV vaccines as the price for 9-valent vaccine was still uncertain. Multicohort immunization strategy was cost-effective in the age range 9–14 years but the upper age limit at which vaccination was no longer cost-effective needs to be further investigated. Key influential parameters identified were duration of vaccine protection, vaccine price, coverage, and discounting rates.ConclusionsThese findings are expected to support policy-makers in making recommendations for HPV immunization programs on either switching to the 9-valent vaccine or inclusion of adolescent boys’ vaccination or extending the age of vaccination.     

Coverage and compliance MDA programme for lymphatic filariasis in Bidar district,Karnataka, India

ObjectiveTo describe the socio demographic characteristics of beneficiaries of the Mass Drug Administration (MDA) programme, to assess the coverage, compliance and causes for noncompliance towards MDA in the district, to assess the awareness regarding elephantiasis among beneficiaries and to assess the knowledge of drug distributors towards the filariasis and MDA programme.MethodsThis cross sectional study was conducted in 3 rural and 1 urban clusters in Bidar district for the period of 1 week. 50 houses were selected in each cluster by systematic random sampling method and data was collected in a structured proforma by interview technique.ResultsMajority of beneficiaries were at the age group of 15-60 years (72.3%) and male (53%). The overall coverage of MDA in Bidar district was 62.3%. Compliance among those who had received the tablets was 60.4%. Coverage and compliance was more in rural areas compared to urban. The most common reason quoted for not consuming drugs was fear of adverse effects (72.2%) The incidence of adverse events was 0.2%. Even though 75% of them were aware of the disease elephantiasis, only 45.4% had knowledge regarding MDA programme. The knowledge of drug distributors towards MDA and filariasis was found to be adequate.ConclusionCoverage and compliance towards MDA in Bidar district was poor. The coverage and compliance in rural areas was higher compared to the urban areas.     

Smoking in China: findings of the 1996 National Prevalence Survey.

CONTEXT: As the world's largest producer and consumer of tobacco products, China bears a large proportion of the global burden of smoking-related disease and may be experiencing a tobacco epidemic. OBJECTIVE: To develop an evidence-based approach supporting tobacco control initiatives in China. DESIGN AND SETTING: A population-based survey consisting of a 52-item questionnaire that included information on demographics, smoking history, smoking-related knowledge and attitudes, cessation, passive smoke exposure, and health status was administered in 145 disease surveillance points in the 30 provinces of China from March through July 1996. PARTICIPANTS: A nationally representative random sample of 128766 persons aged 15 to 69 years were asked to participate; 120298 (93.8%) provided data and were included in the final analysis. About two thirds of those sampled were from rural areas and one third were from urban areas. MAIN OUTCOME MEASURES: Current smoking patterns and attitudes; changes in smoking patterns and attitudes compared with results of a previous national survey conducted in 1984. RESULTS: A total of 41187 respondents smoked at least 1 cigarette per day, accounting for 34.1% of the total number of respondents, an increase of 3.4 percentage points since 1984. Current smoking continues to be prevalent among more men (63%) than women (3.8%). Age at smoking initiation declined by about 3 years for both men and women (from 28 to 25 years). Only a minority of smokers recognized that lung cancer (36%) and heart disease (4%) can be caused by smoking. Of the nonsmokers, 53.5% were exposed to environmental tobacco smoke at least 15 minutes per day on more than 1 day per week. Respondents were generally supportive of tobacco control measures. CONCLUSION: The high rates of smoking in men found in this study signal an urgent need for smoking prevention and cessation efforts; tobacco control initiatives are needed to maintain or decrease the currently low smoking prevalence in women.