A key step toward the discovery of a gene related to a trait is the finding of an association between the trait and one or more haplotypes. Haplotype analyses can also provide critical information regarding the function of a gene; however, when unrelated subjects are sampled, haplotypes are often ambiguous because of unknown linkage phase of the measured sites along a chromosome. A popular method of accounting for this ambiguity in case-control studies uses a likelihood that depends on haplotype frequencies, so that the haplotype frequencies can be compared between the cases and controls; however, this traditional method is limited to a binary trait (case vs. control), and it does not provide a method of testing the statistical significance of specific haplotypes. To address these limitations, we developed new methods of testing the statistical association between haplotypes and a wide variety of traits, including binary, ordinal, and quantitative traits. Our methods allow adjustment for nongenetic covariates, which may be critical when analyzing genetically complex traits. Furthermore, our methods provide several different global tests for association, as well as haplotype-specific tests, which give a meaningful advantage in attempts to understand the roles of many different haplotypes. The statistics can be computed rapidly, making it feasible to evaluate the associations between many haplotypes and a trait. To illustrate the use of our new methods, they are applied to a study of the association of haplotypes (composed of genes from the human-leukocyte-antigen complex) with humoral immune response to measles vaccination. Limited simulations are also presented to demonstrate the validity of our methods, as well as to provide guidelines on how our methods could be used.

Within 2 months of its discovery last spring, a novel influenza A (H1N1) virus, currently referred to as 2009 H1N1, caused the first influenza pandemic in decades. The virus has caused disproportionate disease among young people with early reports of virulence similar to that of seasonal influenza. This clinical review provides an update encompassing the virology, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of the 2009 H1N1 virus. Because information about this virus, its prevention, and treatment are rapidly evolving, readers are advised to seek additional information. We performed a literature search of PubMed using the following keywords: H1N1, influenza, vaccine, pregnancy, children, treatment, epidemiology, and review. Studies were selected for inclusion in this review on the basis of their relevance. Recent studies and articles were preferred.

The success of vaccination programs is contingent upon irrefutable scientific safety data combined with high rates of public acceptance and population coverage. Vaccine hesitancy, characterized by lack of confidence in vaccination and/or complacency about vaccination that may lead to delay or refusal to vaccinate despite the availability of services, threatens to undermine the success of COVID-19 vaccination programs. The rapid pace of vaccine development, misinformation in popular and social media, the polarized sociopolitical environment, and the inherent complexities of large-scale vaccination efforts may undermine vaccination confidence and increase complacency about COVID-19 vaccination. While the experience of recent lethal surges of COVID-19 infections have underscored the value of COVID-19 vaccines, ensuring population uptake of COVID-19 vaccination will require application of multi-level, evidence-based strategies to influence behavior change and address vaccine hesitancy. Recent survey research evaluating public attitudes in the U.S. toward the COVID-19 vaccine reveals substantial vaccine hesitancy. Building upon efforts at the policy and community level to ensure population access to COVID-19 vaccination, a strong healthcare system response is critical to address vaccine hesitancy. Drawing on the evidence base in social, behavioral, communication, and implementation science, we review, summarize and encourage use of interpersonal, individual-level, and organizational interventions within clinical organizations to address this critical gap and improve population adoption of COVID-19 vaccination.

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This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.

WHAT'S KNOWN ON THIS SUBJECT: The reasons why teens are not immunized are related to parental lack of knowledge and the need for provider recommendations. WHAT THIS STUDY ADDS:The reasons for vaccine refusal for human papillomavirus vaccine differ from other teen vaccines, and concerns about its safety are increasing over time.abstract OBJECTIVE: To determine the reasons adolescents are not vaccinated for specific vaccines and how these reasons have changed over time. METHODS:We analyzed the 2008-2010 National Immunization Survey of Teens examining reasons parents do not have their teens immunized. Parents whose teens were not up to date (Not-UTD) for Tdap/Td and MCV4 were asked the main reason they were not vaccinated. Parents of female teens Not-UTD for human papillomavirus vaccine (HPV) were asked their intent to give HPV, and those unlikely to get HPV were asked the main reason why not. RESULTS:The most frequent reasons for not vaccinating were the same for Tdap/Td and MCV4, including "Not recommended" and "Not needed or not necessary." For HPV, the most frequent reasons included those for the other vaccines as well as 4 others, including "Not sexually active" and "Safety concerns/Side effects." "Safety concerns/Side effects" increased from 4.5% in 2008 to 7.7% in 2009 to 16.4% in 2010 and, in 2010, approaching the most common reason "Not Needed or Not Necessary" at 17.4% (95% CI: 15.7-19.1). Although parents report that health care professionals increasingly recommend all vaccines, including HPV, the intent to not vaccinate for HPV increased from 39.8% in 2008 to 43.9% in 2010 (OR for trend 1.08, 95% CI: 1.04-1.13).CONCLUSIONS: Despite doctors increasingly recommending adolescent vaccines, parents increasingly intend not to vaccinate female teens with HPV. The concern about safety of HPV grew with each year. Addressing specific and growing parental concerns about HPV will require different considerations than those for the other vaccines. Dr Darden conceptualized and designed the study, participated in the analyses, drafted the initial manuscript, and approved the final manuscript as submitted. Dr Thompson helped with the design of the study, designed the analytic plan, oversaw the analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. Mrs Hale carried out the analyses, interpreted results, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr Roberts helped with the design of the study, interpreted results, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr Naifeh interpreted results, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr Pope helped with the design of the study, interpreted results, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr Jacobson helped with the design of the study, interpreted results, reviewed and revised the manuscript, and approved the final manuscript as submitted.(Continued on last page) PEDIA...

Patient reminder and recall systems, in primary care settings, are likely to be effective at improving the proportion of the target population who receive immunizations.

Background-Individuals with asthma have been reported to be at increased risk of invasive pneumococcal disease. These findings need to be confirmed in a different population-based study setting.