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Abstract Background Alzheimer's disease, a common dementia of the elder, is characterized by accumulation of protein amyloid deposits in the brain. Immunization to prevent this accumulation has been proposed as a therapeutic possibility, although adverse inflammatory reactions in human trials indicate the need for novel vaccination strategies. Method Here vaccination with novel amyloid peptide immunogens was assessed in a transgenic mouse model displaying age-related accumulation of fibrillar plaques. Results Immunization with any conformation of the amyloid peptide initiated at 12 months of age (at which time fibrillar amyloid has just begun to accumulate) showed significant decrease in total and fibrillar amyloid deposits and in glial reactivity relative to control transgenic animals. In contrast, there was no significant decrease in amyloid deposition or glial activation in mice in which vaccination was initiated at 16 months of age, despite the presence of similar levels anti-Aβ antibodies in young and old animals vaccinated with a given immunogen. Interestingly, immunization with an oligomeric conformation of Aβ was equally as effective as other amyloid peptides at reducing plaque accumulation. However, the antibodies generated by immunization with the oligomeric conformation of Aβ have more limited epitope reactivity than those generated by fAβ, and the microglial response was significantly less robust. Conclusion These results suggest that a more specific immunogen such as oligomeric Aβ can be designed that achieves the goal of depleting amyloid while reducing potential detrimental inflammatory reactions. In addition, the data show that active immunization of older Tg2576 mice with any amyloid conformation is not as efficient at reducing amyloid accumulation and related pathology as immunization of younger mice, and that serum anti-amyloid antibody levels are not quantitatively related to reduced amyloid-associated pathology.

Adult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene, Sry , was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.IMPORTANCEFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females., Competing Interests: The authors declare no conflict of interest.

Purpose: The US Preventive Services Task Force (USPSTF) is an independent body that makes evidence-based recommendations regarding preventive services to improve health for people nationwide. Here, we summarize current USPSTF methods, describe how methods are evolving to address preventive health equity, and define evidence gaps for future research., Methods: We summarize current USPSTF methods as well as ongoing methods development., Results: The USPSTF prioritizes topics on the basis of disease burden, extent of new evidence, and whether the service can be provided in primary care and going forward will increasingly consider health equity. Analytic frameworks specify the key questions and linkages connecting the preventive service to health outcomes. Contextual questions provide information on natural history, current practice, health outcomes in high-risk groups, and health equity. The USPSTF assigns a level of certainty to the estimate of net benefit of a preventive service (high, moderate, or low). The magnitude of net benefit is also judged (substantial, moderate, small, or zero/negative). The USPSTF uses these assessments to assign a letter grade from A (recommend) to D (recommend against). I statements are issued when evidence is insufficient., Conclusions: The USPSTF will continue to evolve its methods for simulation modeling and to use evidence to address conditions for which there are limited data for population groups who bear a disproportionate burden of disease. Additional pilot work is underway to better understand the relations of the social constructs of race, ethnicity, and gender with health outcomes to inform the development of a USPSTF health equity framework., (© 2023 Annals of Family Medicine, Inc.)

Introduction: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States. To date, there has been scant research on how VHA adopts clinical preventive services guidelines and how U.S. Preventive Services Task Force recommendations factor into the process., Methods: Researchers conducted semistructured interviews with eight VHA leaders to examine how they adopt, disseminate, and measure adherence to recommendations. Interviews were recorded, transcribed, and aggregated into a database to enable sorting and synthesis. Themes were identified across the key informant interviews., Results: The development of VHA clinical prevention guidelines is coordinated by the National Center for Health Promotion and Disease Prevention. A VHA Advisory Committee discusses and votes to approve or disapprove each guideline. Several factors can impact the ability of a veterans affairs medical center to implement a guideline, such as local system capacity and priorities for quality improvement. Methods to promote implementation include electronic reminders, educational events, and a robust performance measurement system., Conclusions: Provision of evidence-based clinical preventive services is an important part of VHA's effort to provide high-quality care for Veterans. Recent achievements in lung cancer, colorectal cancer, and Hepatitis C screening highlight VHA's successful approach to implementation of preventive services guidance.

Introduction: Health systems now employ more than half of U.S. physicians. They have the potential to affect primary care through decision support and financial incentives around clinical prevention guidelines. The processes by which they respond to and implement clinical guidelines remain largely unexplored., Methods: In 2015, the research team conducted and analyzed interviews with quality leaders from eight hospital-based systems and one physician organization which together employ >33,000 physicians and serve >15 million patients. Executives explained organizational processes to adapt, adopt, disseminate, and incentivize adherence to preventive services guidelines., Results: Nearly all have a formal process for reviewing and refining guidelines, developing clinician support, and disseminating the approved guidelines. Internal and external factors like organizational structure, patient demographics, and payer contracts affect the review processes and resulting guideline adaptations. Challenges to guideline uptake include competing demands on clinician time and the absence of accurate and timely patient data in accessible and user-friendly formats. Interviewees reported that engaging clinicians in guideline review is critical to successful implementation. Electronic health record reminders represent the primary tool for guideline dissemination and reinforcement. Interviewees reported widespread use of performance monitoring and feedback to clinicians, with varying levels of success. Most organizations use financial incentives tied to performance for some of their clinicians, although details vary widely depending on network structures and contractual arrangements., Conclusions: Health systems play a critical intermediary role between guideline-developing organizations and practicing clinicians. Strengthening the adoption of guidelines requires attention to many factors beyond care delivery., (Copyright © 2017 American Journal of Preventive Medicine. All rights reserved.)

The U.S. Preventive Services Task Force (USPSTF) makes recommendations about clinical preventive services. The USPSTF examines chains of direct and indirect evidence to demonstrate the effectiveness of a clinical preventive service. Missing links across the chains of evidence reflect gaps in the research. Evidence gaps can occur for preventive services that receive a letter grade recommendation and those that receive an I statement (insufficient evidence). This article describes the types of evidence gaps that the USPSTF encounters across its various recommendations and how the USPSTF identifies and communicates these gaps to researchers and policymakers, who can help generate the needed evidence. Common types of evidence gaps include limited evidence in primary care settings and populations, a lack of appropriate health outcomes, limited evidence linking behavior change to health outcomes, and a lack of evidence for effective preventive services in diverse populations. The USPSTF annual report to Congress focuses on the evidence gaps of new recommendations from the past year and is sent to leading research funding agencies. The Office of Disease Prevention at NIH uses this report to help direct future funding opportunities that may address these evidence gaps. The USPSTF plays a critical role in highlighting the information needed to advance the science to optimize the use of clinical preventive services in primary care., (Published by Elsevier Inc.)

The U.S. Preventive Services Task Force (USPSTF) uses an objective evidence-based approach to develop recommendations. As part of this process, the USPSTF also identifies important research gaps in scientific evidence. In March 2016, the USPSTF convened an expert panel to discuss its portfolio of child and adolescent recommendations and identify unique methodologic issues when evaluating evidence regarding children and adolescents. The panel identified key domains of challenges, including measuring patient-centered health outcomes; identifying intermediate outcomes predictive of important health outcomes; evaluating the long time horizon needed to assess the balance of benefits and harms; understanding trajectories of growth and development that result in unique windows of time when expected benefits or harms of a preventive service can vary; and considering the perspectives of other individuals who might be affected by the delivery of a preventive service to a child or adolescent. Although the expert panel expressed an interest in being able to make more recommendations for or against preventive services for children and adolescents, it also reinforced the importance of ensuring recommendations were based on sound and sufficient evidence to ensure greatest benefit and minimize unnecessary harms. Accordingly, the need to highlight areas with insufficient evidence is as important as making recommendations. Having identified these key challenges, the USPSTF and other organizations issuing guidelines have an opportunity to advance their methods of evidence synthesis and identified evidence gaps represent important opportunities for researchers and policy makers., (Copyright © 2017 American Journal of Preventive Medicine. All rights reserved.)

There has been a surge of interest in using 1 type of risk assessment instrument to tailor treatment to juveniles to reduce recidivism. Unlike prediction-oriented instruments, these reduction-oriented instruments explicitly measure variable risk factors as "needs" to be addressed in treatment. There is little evidence, however, that the instruments accurately measure specific risk factors. Based on a sample of 237 serious juvenile offenders (M age = 18, SD = 1.6), we tested whether California Youth Assessment Inventory (CA-YASI) scores validly assess the risk factors they purport to assess. Youth were assessed by practitioners with good interrater reliability on the CA-YASI, and by research staff on a battery of validated, multimethod criterion measures of target constructs. We meta-analytically tested whether each CA-YASI risk domain score (e.g., Attitudes) related more strongly to scores on convergent measures of theoretically similar constructs (e.g., criminal thinking styles) than to scores on discriminant measures of theoretically distinct constructs (e.g., intelligence, somatization, and pubertal status). CA-YASI risk domain scores with the strongest validity support were those that assess criminal history. The only variable CA-YASI risk domain score that correlated more strongly with convergent (Zr = .35) than discriminant (Zr = .07) measures was Substance Use. There was little support for the construct validity of the remaining 6 variable CA-YASI risk domains-including those that ostensibly assess strong risk factors (e.g., "Attitudes," "Social Influence"). Our findings emphasize the need to test the construct validity of reduction-oriented instruments-and refine instruments to precisely measure their targets so they can truly inform risk reduction. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Although increasingly complex risk assessment tools are being marketed, little is known about "real world" practitioners' capacity to score them accurately. In this study, we assess the extent to which 78 staff members' scoring of juveniles on the California-Youth Assessment and Screening Instrument (CA-YASI; Orbis Partners, Inc., 2008) agree with experts' criterion scores for those cases. There are 3 key findings. First, at the total score level, practitioners manifest limited agreement (M ICC = .63) with the criterion: Only 59.0% of staff scores the tool with "good" accuracy. Second, at the subscale level, practitioners' accuracy is particularly weak for treatment-relevant factors that require substantial judgment-like procriminal attitudes (M ICC = .52)-but good for such straightforward factors as legal history (M ICC = .72). Third, practitioners' accuracy depended on their experience-relatively new staff's scores were more consistent with the criterion than those with greater years of experience. Results suggest that attention to parsimony (for tools) and meaningful training and monitoring (for staff) are necessary to realize the promise of risk assessment for informing risk reduction. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

An important component of routine preventive care for children is the monitoring of growth and development. Although cognitive, affective, and behavioral health problems are commonly encountered in pediatric primary care, there is debate around issues related to early detection of significant problems of this type, including the accuracy of screening and the benefits and harms of early diagnosis and treatment. The U.S. Preventive Services Task Force makes recommendations regarding clinical preventive services for primary care clinicians based on the best available scientific evidence. The Task Force has found important gaps related to the validity of commonly used screening tools and significant gaps related to the evidence regarding early treatment. This review describes the meaning of the grades used by the Task Force, how these grades are determined, and the grades assigned to childhood cognitive, affective, and behavioral health recommendations. The review summarizes common themes in the evidence gaps and the future research necessary to advance the field and improve child health outcomes., (Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.)