Antibody persistence and evidence of immune memory at 5 years following administration of the 9-valent HPV vaccine

BackgroundThe 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11/16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPV-related vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the generation of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5 years post-vaccination.MethodsA subset of subjects (N = 150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28 days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card.ResultsHPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1 week and 1 month post-dose 4 were 1.25–4.10 and 1.65–4.88-fold higher, respectively, than levels observed 1 month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1 week and 1 month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated.ConclusionsA three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5 years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting.Clinical Trials.gov Identifier: NCT00543543.     

Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine

ObjectivesTo assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine.MethodsV503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12–26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n = 618) or saline placebo (n = 306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA).ResultsThe frequency of injection-site AEs (days 1–5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1–15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV = 0.5%; placebo = 0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown.ConclusionsAdministration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12–26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated.     

Association of both consistency and strength of self-reported clinician recommendation for HPV vaccination and HPV vaccine uptake among 11- to 12-year-old children

PurposeWe tested the hypotheses that consistency and strength of clinician recommendation of the human papillomavirus (HPV) vaccination would be associated with vaccine delivery rates.MethodsFrom October 2015 through January 2016, we conducted a survey of primary care clinicians (n = 227) in Southeastern Minnesota to evaluate clinician behaviors regarding HPV vaccination. The survey response rate was 41.0% (51 clinical sites). We used the Rochester Epidemiology Project, a clinical data linkage infrastructure, to ascertain clinical site-level HPV vaccination rates. We examined associations of clinician self-reports of both the consistency and strength of their recommendations for HPV vaccination for patients aged 11–12 years (n = 14,406) with site-level vaccination rates.ResultsThe majority of clinicians reported consistently (always or usually) recommending the HPV vaccine to females (79.0%) and to males (62.2%); 71.9% of clinicians reported strongly recommending the vaccine to females while 58.6% reported strongly recommending to males. Consistency and strength of recommending the HPV vaccine was significantly higher among those practicing in pediatrics and board certified in pediatrics compared to family medicine. Higher rates of initiation (1 dose) [Incidence Rate Ratio (IRR) = 1.05; 95% CI (1.01–1.09)] and completion (3 doses) [IRR = 1.08; 95% CI (1.02–1.13)] were observed among clinical sites where, on average, clinicians more frequently reported always or usually recommending the vaccine for females compared to sites where, on average, clinicians reported recommending the vaccine less frequently. Similarly, higher rates of initiation [IRR = 1.03; 95% CI (1.00–1.06)] and completion [IRR = 1.04; CI (1.00, 1.08)] were observed among sites where clinicians reported strongly recommending the vaccine to females more frequently compared to sites where, on average, clinicians reported strongly recommending the HPV vaccine less frequently; similar associations were observed for male initiation [IRR = 1.05; CI (1.02,1.08)] and completion [IRR = 1.05; 95% CI (1.01, 1.09)].ConclusionsConsistency and strength of HPV vaccination recommendation was associated with higher vaccination rates.     

Improving adolescent HPV vaccination in a randomized controlled cluster trial using the 4 Pillars™ practice Transformation Program

ObjectiveUptake of meningococcal vaccine (MCV) and tetanus, diphtheria and pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020 goals, but human papillomavirus (HPV) vaccination has not. This study evaluated an intervention using the 4 Pillars™ Practice Transformation Program to increase HPV, MCV and Tdap uptake among adolescents in primary care practices.MethodsPractices with at least 50 patients 11–17 years old with estimated vaccination rates less than national goals, were assigned to intervention (n = 11) and control (n = 11) groups in a randomized controlled cluster trial; 9 intervention and 11 control sites completed the study. The baseline and active study periods were 7/1/2013–6/30/2014 and 7/1/2014–3/31/2015, respectively. Vaccination and demographic data for patients who had a visit in both study periods were derived from de-identified EMR extractions. Primary outcomes were vaccination rates and percentage point (PP) changes. Data were analyzed in 2015–16.ResultsAmong the cohort of 10,861 adolescent patients, 38% were 11–13 years old; 50% were female; 18% were non-white; and 64% were commercially insured. Average baseline HPV initiation rates were 52.5% for intervention and 61.8% for control groups. After 9 months, the intervention sites increased HPV initiation 10.2 PP compared with 7.3 PP in control sites (P < 0.001); HPV series completion rates did not differ between groups. Implementation of >10 strategies to improve rates significantly increased the likelihood of HPV series initiation (OR = 2.06, 95% CI = 1.43, 2.96).ConclusionsUsing >10 strategies from the 4 Pillars™ Practice Transformation Program is effective for increasing HPV series initiation among adolescents.Clinical trial registry number: NCT02165722.     

Age at HPV vaccine initiation and completion among US adolescent girls: Trend from 2008 to 2012

ObjectiveTo examine the trend of provider-verified HPV vaccine initiation (≥1 dose) and completion (≥3 doses) among adolescent girls at the Advisory Committee on Immunization Practices (ACIP) recommended age (11–12 years).MethodsWe analyzed National Immunization Survey of Teens 2008–2012 data and examined the trend of provider-verified HPV vaccine initiation and completion among <13 year old girls.ResultsData on age at HPV vaccine initiation and completion were available for 24,466 and 15,972 girls, respectively. The weighted proportion of girls who initiated the vaccine at <13 years of age was 14.1%, 24.1%, 35.9%, 47.7% and 55.9% in 2008, 2009, 2010, 2011 and 2012, respectively (p for trend <.001). The similar trend was also observed for mean age at HPV vaccine initiation and completion (p < .001).ConclusionsAdditional efforts are needed to increase HPV vaccine uptake among adolescent girls as only half of them receive this vaccine at ACIP recommended age.     

Risk of Guillain-Barré Syndrome following quadrivalent human papillomavirus vaccine in the Vaccine Safety Datalink

ObjectiveDescribe the Vaccine Safety Datalink’s (VSD) Guillain Barré Syndrome (GBS) surveillance following quadrivalent HPV vaccine (4vHPV) from 2006 through 2015.MethodsAmong 4vHPV vaccinated persons aged 9–26, ICD-9 coded GBS was identified in VSD’s electronic data. Medical records were reviewed and adjudicated to confirm GBS. We calculated incidence rates of confirmed GBS within 1–42 days following 4vHPV with a one-sided 95% confidence interval.ResultsFollowing 2,773,185 4vHPV doses, we confirmed 1 case of GBS in a male and no cases among females. The incidence rate of medical record confirmed GBS within 42 days following 4vHPV vaccine was 0.36 cases per million 4vHPV doses administered (1-sided 95% CI 1.71), which was less than the background rate.ConclusionWe found no evidence of an increased risk of GBS following 4vHPV. With an upper 95% confidence limit, we estimate that, if an increased risk exists, we would expect at most 1.08 additional cases of GBS per million people vaccinated with 4vHPV.     

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men

BackgroundA nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16–26-year-old men.MethodsParticipants (N = 500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed.ResultsThe HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles.ConclusionsIn addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16–26 years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16–26 years.NCT02114385     

Trends in prolonged sitting time among European adults: 27 country analysis

ObjectiveTo examine trends in adult sitting time across 27 European countries.MethodData were from the Eurobarometer surveys collected in 2002, 2005, and 2013. Sitting time data were used to categorise respondents into ‘low’ (0 to 4h30min), ‘middle’ (4h31min to 7h30min), and ‘high’ levels of sitting (>7h30min). We modelled the likelihood of being in the high sitting group within a given country and overall across the three time points, controlling for age, gender, education, employment status, and physical activity.ResultsIn total 17 countries had sitting data at all three time points; among these countries the prevalence of ‘high sitting’ decreased steadily from 23.1% (95% CI = 22.2–24.1) in 2002 to 21.8% (95% CI = 20.8–22.8) in 2005, and 17.8% (95% CI = 16.9–18.7) in 2013. A further 10 countries had data only over the latter two time points; among these countries the prevalence of high sitting decreased from 27.7% (95% CI = 26.0–29.4) in 2005 to 19.0% (95% CI = 17.6–20.5) in 2013.ConclusionTime spent in sedentary behaviour may not be increasing in the European region, and prolonged sitting may, in fact, be decreasing. This finding has important implications for the sedentary behaviour debate and the policy response.     

Lack of association between Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms and tuberculosis susceptibility: A meta-analysis

ObjectiveToll-like receptor 4 (TLR4) plays a vital role in immunity to tubercle bacillus and its gene polymorphisms are supposed to affect tuberculosis susceptibility in some rather than all studies. Then, we integrated published data and performed a comprehensive meta-analysis to get more reliable estimations for the strength of associations between TLR4 gene polymorphisms and the risk of tuberculosis.MethodsWe systematically searched the electronic PubMed database for research articles about TLR4 gene polymorphisms and tuberculosis up to February 2012. Revman 5.0 software was adopted to conduct the meta-analysis. Crude odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by either fixed-effects model or random-effects model.ResultsFinally, six case-control studies were identified, involving 1587 controls and 2110 patients. Overall, no significant associations were found between TLR4 gene Asp299Gly polymorphism and tuberculosis in the codominant models (GG vs AA: OR = 1.56, 95% CI = 0.76–3.21, P = 0.23; GA vs AA: OR = 1.01, 95% CI = 0.84–1.23, P = 0.89), the dominant model (GG + GA vs AA: OR = 1.04, 95% CI = 0.80–1.35, P = 0.75), the recessive model (GG vs GA + AA: OR = 1.55, 95% CI = 0.75–3.19, P = 0.24) and the allele model (G vs A: OR = 1.06, 95% CI = 0.81–1.40, P = 0.66). Similarly, no significant associations between TLR4 gene Thr399Ile and tuberculosis were observed (all P > 0.05).ConclusionsThe present meta-analysis suggests that TLR4 gene Asp299Gly and Thr399Ile polymorphisms are not associated with the susceptibility of tuberculosis.     

Clinician knowledge,clinician barriers,and perceived parental barriers regarding human papillomavirus vaccination: Association with initiation and completion rates

PurposeWe tested the hypothesis that clinician knowledge, clinician barriers, and perceived parental barriers relevant to the human papillomavirus (HPV) vaccination account for the variation in vaccine delivery at the practice-site level.MethodsWe conducted a survey from October 2015 through January 2016 among primary care clinicians (n = 280) in a 27-county geographic region to assess clinician knowledge, clinician barriers, and perceived parental barriers regarding HPV vaccination. Primary care clinicians included family medicine physicians, general pediatricians, and family and pediatric nurse-practitioners. We also used the Rochester Epidemiology Project to measure HPV vaccination delivery. Specifically we used administrative data to measure receipt of at least one valid HPV vaccine dose (initiation) and receipt of three valid HPV vaccine doses (completion) among 9–18 year old patients residing in the same 27-county geographic region. We assessed associations of clinician survey data with variation in vaccine delivery at the clinical site using administrative data on patients aged 9–18 years (n = 68,272).ResultsConsistent with our hypothesis, we found that greater knowledge of HPV and the HPV vaccination was associated with higher rates of HPV vaccination initiation (Incidence rate ratio [IRR] = 1.05) and completion of three doses (IRR = 1.28). We also found support for the hypothesis that greater perceived parental barriers to the HPV vaccination were associated with lower rates of initiation (IRR = 0.94) and completion (IRR = 0.90). These IRRs were statistically significant even after adjustment for site-level characteristics including percent white, percent female, percent ages 9–13, and percent with government insurance or self-pay at each site.ConclusionsClinician knowledge and their report of the frequency of experiencing parental barriers are associated with HPV vaccine delivery rates—initiation and completion. Higher measures of knowledge correlated with higher rates. Fewer perceived occurrences of parental barriers correlated with lower rates. These data can guide efforts to improve HPV vaccine delivery in clinical settings.     

Correlates between risk perceptions of cervical cancer and screening practice

ObjectivesTo identify the correlates between risk perceptions and cervical cancer screening among urban Malaysian women.MethodA cross-sectional household survey was conducted among 231 women in Petaling Jaya city in 2007. The association of risk perceptions of cervical cancer and screening practice was analyzed using Poisson regression.Results56% of the respondents ever had a Pap smear test. Knowledge of signs and symptoms (aPR = 1.11, 95% CI = 1.03–1.19), age (aPR = 1.02, 95% CI = 1.01–1.03), number of pregnancies (aPR = 1.06, 95% CI = 1.01–1.11), marital status, education level and religion were found to be significant correlates of Pap smear screening. Respondents who were never married were less likely to have had a Pap smear. Those who had no education or primary education were less likely to have had a Pap smear compared to those with degree qualification. The prevalence of screening was significantly higher among Christians and others (aPR = 1.35; 95% CI = 1.01–1.81) and Buddhists (aPR = 1.38; 95% CI = 1.03–1.84), compared to Muslims.ConclusionEliminating anecdotal beliefs as risks via targeted knowledge on established risk factors and culturally sensitive screening processes are strategic for increasing and sustaining uptake of Pap smear screening versus current opportunistic screening practices.     

Facteurs sociodémographiques et recours aux soins pour raisons psychologiques chez les jeunes adultes

BackgroundAlthough young adults exhibit a high rate of psychiatric disorders, their rate of access to mental health care is low compared with older age groups. Our study examined the relationship between socio-demographic factors and the use of health care services for psychological reasons.MethodsWe studied a community sample of 1103 French 22 to 35-year-old (TEMPO cohort study) who were surveyed by mailed questionnaire in 2009. Data were collected regarding participants’ health (internalizing and externalizing psychological symptoms in 1991 and 2009), health care use (access to health professionals and psychotropic medications in case of psychological difficulties), and socio-demographic factors (sex, age, employment status, marital situation, social support). Parental history of depression was ascertained based on TEMPO participants’ and their parents’ reports (in the GAZEL cohort study).ResultsIn the 12 months preceding the study, 16.7% of study participants saw a health professional and 12.8% took a psychotropic medication for psychological reasons. In multivariate regression, models adjusted for all socio-demographic and psychological characteristics, access to health professionals was associated with being unemployed/out of the labor force (OR = 1.93; 95% CI = 1.11–3.30), family situation (OR in participants living with a partner with no children: 2.16; 95% CI 1.26–3.72; OR in participants not living with a partner: 2.29; 95% CI = 1.34–3.90), and having low social support (OR = 1.75; 95% CI = 1.21–2.54). The use of psychotropic medications was associated with female gender (OR = 2.70; 95% CI = 1.60–4.55), being unemployed/out of the labor force (OR = 3.85; 95% CI = 2.14–6.95), not living with a partner (OR = 2.04; 95% CI = 1.09–3.80) and having low social support (OR = 1.65; 95% CI = 1.05–2.59). Additionally, use of health services was associated with participants’ and their parents’ psychological difficulties.     

Annual influenza vaccination reduces total hospitalization in patients with chronic hepatitis B virus infection: A population-based analysis

BackgroundThis study evaluated hospitalization and mortality in patients with chronic hepatitis B virus infection (HBV (+)) and matched comparison patients after stratifying the patients according to annual influenza vaccination (Vaccine (+)).MethodsData from Taiwan's National Health Insurance program from 2000 to 2009 were used to identify HBV(+)/vaccine(+) (n = 4434), HBV(+)/Vaccine(−) (n = 3646), HBV(−)/Vaccine(+) (n = 8868), and HBV(−)/Vaccine(−) (n = 8868) cohorts. The risk of pneumonia/influenza, respiratory failure, intensive care, hospitalization, and mortality in the four cohorts was evaluated.ResultsThe total hospitalization rate was significantly lower in patients with chronic HBV infection who received an annual influenza vaccination than in chronic HBV-infected patients who did not receive an influenza vaccination (16.29 vs. 24.02 per 100 person-years), contributing to an adjusted hazard ratio (HR) of 0.56 (95% confidence interval (CI) = 0.50–0.62). The HBV(+)/Vaccine(+) cohort also had lower risks than the HBV(+)/Vaccine(−) cohort for pneumonia and influenza (adjusted HR = 0.79, 95% CI = 0.67–0.92), intensive care unit admission (adjusted HR = 0.33, 95% CI = 0.25–0.43), and mortality (adjusted HR = 0.19, 95% CI = 0.15–0.24).ConclusionsOur results suggest that annual influenza vaccination can reduce the risk of hospitalization and mortality in patients with chronic HBV infection.     

Analysis of TLR4 (Asp299Gly and Thr399Ile) gene polymorphisms and mRNA level in patients with dengue infection: A case-control study

BackgroundDengue is a systemic viral infection that spreads to humans by the bite of infected Aedes mosquitoes. The secreted NS1 protein of dengue virus activates macrophages and human PBMCs via TLR4 and induce the release of pro-inflammatory cytokines which is responsible for the pathogenesis of disease. Mutations in TLR4 gene have been associated with the increased susceptibility to many viral, bacterial and parasitic diseases.ObjectiveTo study the impact of TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791) gene polymorphisms with susceptibility to dengue infection.MethodsA total of 120 dengue infected (57; DHF/DSS and 63; DF) and 200 healthy controls were included in the study. TLR4 Asp299Gly and Thr399Ile gene polymorphisms was studied by PCR-RFLP. Expression of TLR4 mRNA was evaluated by rRT-PCR.ResultsIndividuals with heterozygous genotype for TLR4 Asp299Gly and Thr399Ile polymorphisms had increased susceptibility to dengue infection (OR-1.70, 95% CI = 1.01–2.86 P = 0.042 and OR-2.17, 95% CI = 1.10–4.28, P = 0.024, respectively). The frequency of Gly and Ile alleles were higher in dengue patients as compared to controls (OR-1.67, 95% CI = 1.05–2.64, P = 0.029 and OR-2.20, 95% CI = 1.19–4.07, P = 0.011, respectively). IIe/Gly haplotype was associated with the risk of the disease when compared with controls (OR = 3.15, 95% CI = 1.09–9.09, P = 0.035). The mRNA expression was higher in DF when compared with DHF/DSS and controls (P = 0.040 and 0.009, respectively).ConclusionA higher expression of TLR4 mRNA was associated with DF. The TLR4 Asp299Gly and Thr399Ile gene polymorphisms were associated with the susceptibility of dengue infection probably by altering the immune response.     

The MTHFR C677T mutation is not a risk factor recognized for HBV-related HCC in a population with a high prevalence of this genetic marker

BackgroundPolymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene can affect disease progression in HBV infection. However, the results from different reports are inconsistent. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and the outcome of HBV infection in a Tianjin Han population.MethodsTaqMan SNP genotyping was employed to determine the alleles and genotypes of MTHFR C677T in 2511 subjects from various stages of HBV infection and 549 healthy controls.ResultsOf the 3060 subjects, the genotypic frequencies were CT 48.9%, TT 29.3% and CC 21.8%; the allelic frequencies were T 53.8% and C 46.2%. There was no significant difference in genotypic or allelic distribution among the different disease groups. When either healthy subjects or self-limited subjects were used as controls, the TT genotype and the T allele conferred protective effects against hepatocellular carcinoma (HCC) (HCC vs healthy subjects: OR = 0.588, 95% CI = 0.413–0.836, P = 0.003; OR = 0.768, 95% CI = 0.645–0.915, P = 0.003, respectively. HCC vs self-limited subjects: OR = 0.598, 95% CI = 0.404–0.886, P = 0.010; OR = 0.772, 95% CI = 0.635–0.940, P = 0.010, respectively). After sub-stratification by gender, the prevalence of the TT genotype or T allele was the lowest in the male HCC group (TT 23.5%, T 49.8%). The protective effects of the TT genotype and the T allele were observed in male HCC and cirrhotic subjects (HCC vs self-limited subjects: OR = 0.470, 95% CI = 0.288–0.766, P = 0.002; OR = 0.681, 95% CI = 0.535–0.866, P = 0.002, respectively. Liver cirrhosis vs self-limited subjects: OR = 0.624, 95% CI = 0.392–0.992, P = 0.046; OR = 0.791, 95% CI = 0.627–0.998, P = 0.048, respectively), but not in female. When the subjects were stratified according to the clinical features, no statistically significant difference in the genotypic distribution was observed (P > 0.05).ConclusionsThe TT genotype and T allele of MTHFR C677T may confer a protective effect on disease progression to HCC in HBV-infected individuals, especially among male patients, in a population with a high prevalence of this genetic marker.     

School bullying and susceptibility to smoking among never-tried cigarette smoking students

IntroductionBullying involvement has been linked with substance use; however, less is known about its relationship with pre-initiation stages of adolescent cigarette smoking behavior. This study examined the association between bullying involvement and smoking susceptibility among never tried or experimented with cigarette smoking students. Susceptibility to cigarette smoking in adolescence is a strong predictor of subsequent smoking initiation.MethodsA cross-sectional data on Canadian adolescent and youth were drawn from the 2012/2013 Youth Smoking Survey (n = 28,843). Logistic regression analysis was used to examine the association between bullying and smoking susceptibility among never-smoking students.ResultsAbout 21% self-reported involvement in bullying (as a bully, victim or both). Middle school students (grades 6–8) reported more involvement in bullying (24%) than those in grades 9–12 (16%). The multivariable analyses showed that the association between bullying and smoking susceptibility was significantly different by grade level. Middle school students involved in bullying had higher odds of smoking susceptibility compared to uninvolved students (bully, adjusted odds ratio [AOR] = 2.54, 95% CI = 1.73–3.74; victim, AOR = 1.29, 95% CI = 1.11–1.48; bully–victim, AOR = 2.19, 95% CI = 1.75–2.74). There were no significant associations between all subgroups of bullying and smoking susceptibility for grades 9–12 students.ConclusionsStudents involved in bullying were more susceptible to smoking, although patterns of association varied by grade level. In particular, the findings highlight that non-smoking middle school students involved in bullying were susceptible to future smoking.     

Rabies vaccine is associated with decreased all-cause mortality in dogs

Evidence suggests that rabies vaccine may have non-specific protective effects in animals and children. We analyzed four years of data (2012–2015) from an observational study of the health and demographics of a population of owned, free-roaming dogs in a low-income community in South Africa. The objective of this analysis was to assess the association between rabies vaccine and all-cause mortality in dogs, stratified by age group (0–3 months, 4–11 months, and 12 months and older), and controlling for the effects of sex and number of dogs in the residence. Rabies vaccination reduced the risk of death from any cause by 56% (95% CI = 16–77%) in dogs aged 0–3 months, by 44% (95% CI = 21–60%) in dogs aged 4–11 months and by 16% (95% CI = 0–29%) in dogs aged 12 months and older. We hypothesize that the protective association between rabies vaccination status and all-cause mortality is due to a protective effect of rabies vaccine against diseases other than rabies. Existence of a strong non-specific protective effect of rabies vaccine on mortality in dogs would have implications for the design of dog rabies control programs that aim to eliminate dog-mediated human rabies cases. Further, we propose that owned domestic dogs in high mortality settings provide a useful animal model to better understand any non-specific protective effect of rabies vaccine in children, due to dogs’ high numbers, high morbidity and mortality rates, relatively short lifespan, exposure to a variety of infectious and parasitic diseases, and shared environment with people.     

Suicide in older men: The health in men cohort study (HIMS)

Suicide rates are high in later life, particularly among older men. Mood disorders are known risk factors, but the risk of suicide associated with poor physical health remains unclear. We completed a cohort study of a community representative sample of 38,170 men aged 65–85 in 1996 who were followed for up to 16 years. Data on suicide attempts and completion were obtained from the Western Australia Data Linkage System, as was information about medical and mental health diagnoses. 240 (0.6%) participants had a recorded history of past suicide attempt, most commonly by poisoning (85%). Sixty-nine men died by suicide during follow up (0.3% of all deaths), most often by hanging (50.7%). Age-adjusted competing risk regression showed that past suicide attempt was not a robust predictor of future suicide completion (sub-hazard ratio, SHR = 1.58, 95% CI = 0.39, 6.42), but bipolar (SHR = 7.82, 95% CI = 3.08, 19.90), depressive disorders (SHR = 2.26, 95% CI = 1.14, 4.51) and the number of health systems affected by disease (SHR for 3–4 health systems = 6.02, 95% CI = 2.69, 13.47; SHR for ≥ 5 health systems = 11.18, 95% CI = 4.89, 25.53) were. The population fraction of suicides attributable to having 5 or more health systems affected by disease was 79% (95% CI = 57%, 90%), and for any mood disorder (bipolar or depression) it was 17% (95% CI = 3%, 28%). Older Australian men with multiple health morbidities have the highest risk of death by suicide, even after taking into account the presence of mood disorders. Improving the overall health of the population may be the most effective way of decreasing the rates of suicide in later life.     

Decreased accuracy in interpretation of community-based screening mammography for women with multiple clinical risk factors

ObjectiveTo assess the impact of women's breast cancer risk factors (use of hormone therapy, family history of breast cancer, previous breast biopsy) on radiologists' mammographic interpretive performance and whether the influence of risk factors varies according to radiologist characteristics.Study Design and SettingScreening mammograms (n = 638,947) performed from 1996 to 2005 by 134 radiologists from three Breast Cancer Surveillance Consortium registries was linked to cancer outcomes, radiologist surveys, and patient questionnaires. Interpretive performance measures were modeled using marginal and conditional logistic regression.ResultsHaving one or more clinical risk factors was associated with higher recall rates (1 vs. 0 risk factors: odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.15–1.19; ≥2 vs. 0: OR = 1.43, 95% CI = 1.40–1.47) and lower specificity (1 vs. 0: OR = 0.86 [95% CI = 0.84–0.88]; ≥2 vs. 0: OR = 0.70 [95% CI = 0.68–0.72]) without a corresponding improvement in sensitivity and only a small increase in positive predictive value (1 vs. 0: OR = 1.08 [95% CI = 0.99–1.19]; ≥2 vs. 0: OR = 1.12 [95% CI = 0.99–1.26]). There was no indication that influence of risk factors varied by radiologist characteristics.ConclusionWomen with clinical risk factors who undergo screening mammography are more likely recalled for false-positive evaluation without an associated increase in cancer detection. Radiologists and patients with risk factors should be aware of this increased risk of adverse screening events.