Vacteens.org: A Mobile Web app to Improve HPV Vaccine Uptake

U.S. HPV vaccine uptake remains below the Healthy People 2030 goal of 80% series completion. Parental concerns and misinformation about the efficacy and safety of the Human Papillomavirus (HPV) vaccine remain, and may be addressed by digital interventions tailored to their concerns. Reported here are results from a small scale randomized trial testing a mobile web app for parents and their adolescent daughters (ages 11-14 years) encouraging HPV vaccination in New Mexico, an ethnically-diverse U.S. state. Methods: A clinic-cluster randomized trial where pediatric clinics (n = 9) were recruited and randomized, and parent-adolescent pairs (n = 82) within clinics received either the Vacteens.org/Vacunadolescente.org mobile web app or Usual and Customary (UC) HPV Vaccination information. Parents completed online surveys at baseline and 3-months. Daughters' HPV vaccine data were collected from the New Mexico State Immunization Information System 1 year post baseline. Results: Three month survey results found Vacteens.org/Vacunadolescente.org parents to have higher positive HPV vaccine beliefs, informed decision making, intent to vaccinate and vaccine confidence outcomes than UC parents. HPV vaccine data found higher first dose HPV vaccination (Pearson χ2 = 6.13, p = 0.013, Vacteens.org/Vacunadolescente.org group 59.4%, UC group 40.6%), and higher HPV vaccination series completion (Pearson χ2 = 6.49, p = 0.011, Vacteens.org/Vacunadolescente.org group 68.4%, UC group 31.6%). Conclusions: The small trial results showed the Vacteens.org/Vacunadolescente.org web app prompted positive vaccine-related attitudes and beliefs, and more HPV vaccination initiation and series completion. Mobile web apps can make decision-making tools for HPV vaccination widely available on digital platforms, reducing vaccine hesitancy, and confusion and increase HPV vaccine uptake

Age-period-cohort analysis for trends in body mass index in Ireland

Background: Obesity is a growing problem worldwide and can often result in a variety of negative health outcomes. In this study we aim to apply partial least squares (PLS) methodology to estimate the separate effects of age, period and cohort on the trends in obesity as measured by body mass index (BMI). Methods. Using PLS we will obtain gender specific linear effects of age, period and cohort on obesity. We also explore and model nonlinear relationships of BMI with age, period and cohort. We analysed the results from 7,796 men and 10,220 women collected through the SLAN (Surveys of Lifestyle, attitudes and Nutrition) in Ireland in the years 1998, 2002 and 2007. Results: PLS analysis revealed a positive period effect over the years. Additionally, men born later tended to have lower BMI (-0.026 kg·m-2 yr-1, 95% CI: -0.030 to -0.024) and older men had in general higher BMI (0.029 kg·m -2 yr-1, 95% CI: 0.026 to 0.033). Similarly for women, those born later had lower BMI (-0.025 kg·m-2 yr-1, 95% CI: -0.029 to -0.022) and older women in general had higher BMI (0.029 kg·m-2 yr-1, 95% CI: 0.025 to 0.033). Nonlinear analyses revealed that BMI has a substantial curvilinear relationship with age, though less so with birth cohort. Conclusion: We notice a generally positive age and period effect but a slightly negative cohort effect. Knowing this, we have a better understanding of the different risk groups which allows for effective public intervention measures to be designed and targeted for these specific population subgroups

Host-Directed Therapies for tackling Multi-Drug Resistant TB – learning from the Pasteur-Bechamp debates

Tuberculosis (TB) remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of TB treatment has been on antibiotic development targeting Mycobacterium tuberculosis (M.tb). The lengthy TB treatment duration and poor treatment outcomes associated with multi-drug resistant TB (MDR-TB) are of major concern. The sparse new TB drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the ‘microbe’ versus the ‘host internal milieu’ in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of TB therapy and improving treatment outcomes for drug-susceptible TB and MDR-TB. Funder initiatives that may enable further research into HDTs are described

Mechanistic Insights on the Inhibition of C5 DNA Methyltransferases by Zebularine

In mammals DNA methylation occurs at position 5 of cytosine in a CpG context and regulates gene expression. It plays an important role in diseases and inhibitors of DNA methyltransferases (DNMTs)—the enzymes responsible for DNA methylation—are used in clinics for cancer therapy. The most potent inhibitors are 5-azacytidine and 5-azadeoxycytidine. Zebularine (1-(β-D-ribofuranosyl)-2(1H)- pyrimidinone) is another cytidine analog described as a potent inhibitor that acts by forming a covalent complex with DNMT when incorporated into DNA. Here we bring additional experiments to explain its mechanism of action. First, we observe an increase in the DNA binding when zebularine is incorporated into the DNA, compared to deoxycytidine and 5-fluorodeoxycytidine, together with a strong decrease in the dissociation rate. Second, we show by denaturing gel analysis that the intermediate covalent complex between the enzyme and the DNA is reversible, differing thus from 5-fluorodeoxycytidine. Third, no methylation reaction occurs when zebularine is present in the DNA. We confirm that zebularine exerts its demethylation activity by stabilizing the binding of DNMTs to DNA, hindering the methylation and decreasing the dissociation, thereby trapping the enzyme and preventing turnover even at other sites

The use of a chronic disease and risk factor surveillance system to determine the age, period and cohort effects on the prevalence of obesity and diabetes in South Australian adults--2003-2013

Age, period and cohort (APC) analyses, using representative, population-based descriptive data, provide additional understanding behind increased prevalence rates