Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration.To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus-vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.     

Disparities in Capreomycin Resistance Levels Associated with the rrs A1401G Mutation in Clinical Isolates of Mycobacterium tuberculosis

As the prevalence of multidrug-resistant and extensively drug-resistant tuberculosis strains continues to rise, so does the need to develop accurate and rapid molecular tests to complement time-consuming growth-based drug susceptibility testing. Performance of molecular methods relies on the association of specific mutations with phenotypic drug resistance and while considerable progress has been made for resistance detection of first-line antituberculosis drugs, rapid detection of resistance for second-line drugs lags behind. The rrs A1401G allele is considered a strong predictor of cross-resistance between the three second-line injectable drugs, capreomycin (CAP), kanamycin, and amikacin. However, discordance is often observed between the rrs A1401G mutation and CAP resistance, with up to 40% of rrs A1401G mutants being classified as CAP susceptible. We measured the MICs to CAP in 53 clinical isolates harboring the rrs A1401G mutation and found that the CAP MICs ranged from 8 μg/ml to 40 μg/ml. These results were drastically different from engineered A1401G mutants generated in isogenic Mycobacterium tuberculosis, which exclusively exhibited high-level CAP MICs of 40 μg/ml. These data support the results of prior studies, which suggest that the critical concentration of CAP (10 μg/ml) used to determine resistance by indirect agar proportion may be too high to detect all CAP-resistant strains and suggest that a larger percentage of resistant isolates could be identified by lowering the critical concentration. These data also suggest that differences in resistance levels among clinical isolates are possibly due to second site or compensatory mutations located elsewhere in the genome.     

Lessons learned from a blended telephone/e-health platform for caregivers in promoting physical activity and nutrition in children with a mobility disability

BackgroundChildren with physical disabilities report higher rates of sedentary lifestyle and unhealthy dietary patterns than non-disabled peers. These behaviors can increase comorbidities, caregiver burden, and healthcare costs. Innovative interventions are needed to assist caregivers of children with physical disabilities improve health behaviors.Objective/Hypothesis: The purpose of this pilot study was to test the usability and preliminary efficacy of an e-health and telecoaching intervention compared to telecoaching alone.MethodsParent/child dyads (n = 65) were randomized into either the e-health and telephone group (e-HT) or the telephone only group (TO). All participants received regular calls from a telecoach, and the e-HT group received access to a website with personalized weekly goals for diet and physical activity, and access to resources to meet these goals. At the conclusion of the intervention, participants in the e-HT group were asked to complete a semi-structured interview to discuss the usability of the e-health platform.ResultsFifty of the 65 randomized dyads (77%) completed all baseline measures and had at least one intervention call. Forty families (80% of those that started the intervention) completed the study (50% spina bifida, 24% mobility limitation, diagnosis not reported). Age of the children ranged from 6 to 17 years old. Both groups had high adherence to scheduled phone calls (e-HT (n = 17): 81%, TO (n = 23): 86%); however no significant differences in dietary intake or physical activity were seen within or between groups. Primary themes to emerge from qualitative interviewers were: the platform should target children rather than parents, parents valued the calls more than the website, and schools need to be involved in interventions.ConclusionsE-health interventions are a promising way to promote healthy behaviors in children with physical disability, but technology must be balanced with ease of use for parents while also engaging the child.     

Technology and social media use by adult patients with intellectual and/or developmental disabilities

BackgroundTechnology and social media offer individuals with intellectual and/or developmental disabilities (I/DD) unique and innovative ways to facilitate active participation in their own healthcare process. What remains unclear is the extent to which devices are currently used by this growing patient population.ObjectiveTo explore the prevalence of technology and social media use, as well as the possible barriers, among adult patients with I/DD.MethodsA cross-sectional study utilizing an anonymous, accessible survey was used to obtain data from all adult patients (18 + years of age) with I/DD presenting for primary care services at a healthcare facility in New York between September and December of 2016.ResultsA total of 370 individuals completed the survey (529 approached, 69.9% response rate). Less than half (44.6%) of respondents used devices such as a tablet, smartphone or desktop; most (86.8%) did not use social media. Only 21.6% of respondents indicated that they use some type of assistive technology. While some respondents (46.0%) were identified by their caregivers as having a disability that would prevent them from learning/using technology, other respondents reported having no challenges (18.0%), needing training and/or ongoing support (7.4%), or being uncertain as to whether they would experience any challenges (15.5%).ConclusionsMany adult patients with I/DD do not use technology and social media that could promote self-determination and participation in their healthcare. Continued efforts must be made to promote technology use among adults with I/DD and to ensure that appropriate training is available for both the individual and his/her caregivers to achieve adoption and utilization.     

Declines in Pregnancies among U.S. Adolescents from 2007 to 2017: Behavioral Contributors to the Trend

Study ObjectivesAdolescent pregnancies and births in the United States have undergone dramatic declines in recent decades. We aimed to estimate the contribution of changes in 3 proximal behaviors to these declines among 14- to 18-year-olds for 2007-2017: 1) delays in age at first sexual intercourse, 2) declines in number of sexual partners, and 3) changes in contraceptive use, particularly uptake of long-acting reversible contraception (LARC).DesignWe adapted an existing iterative dynamic population model and parameterized it using 6 waves of the Centers for Disease Control and Prevention's Youth Risk Behavior Survey. We compared pregnancies from observed behavioral trends with counterfactual scenarios that assumed constant behaviors over the decade. We calculated outcomes by cause, year, and age.ResultsWe found that changes in these behaviors could explain pregnancy reductions of 496,200, 78,500, and 40,700 over the decade, respectively, with total medical and societal cost savings of $9.71 billion, $1.54 billion, and $796 million. LARC adoption, particularly among 18-year-olds, could explain much of the improvement from contraception use. The 3 factors together did not fully explain observed birth declines; adding a 50% decline in sex acts per partner did.ConclusionsDelays in first sexual intercourse contributed the most to declining births over this decade, although all behaviors considered had major effects. Differences from earlier models could result from differences in years and ages covered. Evidence-based teen pregnancy prevention programs, including comprehensive sex education, youth-friendly reproductive health services, and parental and community support, can continue to address these drivers and reduce teen pregnancy.     

Disability advocacy messaging and conceptual links to underlying disability identity development among college students with learning disabilities and attention disorders

BackgroundLearning disabilities and attention disorders (LD/AD) are highly prevalent neurodevelopmental conditions that influence developmental trajectories and whose impacts exist throughout the life course. Self-advocacy skills are critical for college students with LD/AD, which are underpinned by understanding of self and one's disability.ObjectiveThis study examined disability advocacy messaging included in projects created by college students with LD/AD, compared patterns in disability messaging to existing disability identity models, and explored changes in disability messaging during receipt of holistic campus-based LD/AD supports.MethodsParticipants were 52 undergraduates with LD/AD enrolled in a larger study. This one-group analysis involved qualitative exploration of the projects’ topical content, use of grounded theory procedures for conceptualizing the data, and quantitative analysis to explore changes over time in disability advocacy messaging.ResultsParticipants messaged a broad range of disability-related topics. A five-level theoretical model of disability messaging was created from the textual data. The model evinces parallels to existing disability identity development models. A significant (p < .01) positive shift in disability messaging was observed in a comparison of messages from participants’ first and last projects submitted over the four-semester period of study involvement.ConclusionStudy findings support conceptual linkages among disability messaging and disability identity development. The resultant continuum model suggests a potential extension of existing disability identity development paradigms. Shifts in disability messaging provide preliminary evidence for potential personal and institutional benefits of engaging college students with LD/AD in disability-focused project creation.     

Spousal support and self-determined physical activity in individuals with multiple sclerosis: A theory-informed qualitative exploration

BackgroundIndividuals with multiple sclerosis (MS) tend to exhibit high levels of sedentary behavior which contributes to increased disability and comorbidity. Understanding what factors underlie the motivation to be physically active in this group is therefore important.ObjectiveThis theory-informed qualitative study explored spousal support and behavior in fostering self-determined physical activity engagement of adults with MS.MethodsEight couples were interviewed using a semi-structured interview guide derived from Self-Determination Theory.ResultsAnalysis of transcribed audio recordings revealed that supportive and empathetic spousal communication, encouragement and expectations regarding physical activity, and bonding through co-participation increased feelings of relatedness. In addition, co-planning and problem-solving around physical activity and serving as a behavioral model facilitated perceptions of competency, while spouses who valued their partners’ independence and offered choice enhanced autonomous motivation for physical activity.ConclusionsInsight into the marital context that supports self-determined physical activity decisions of individuals with MS may better inform family-oriented health promotion approaches in this group.