Linking Angelman and dup15q data for expanded research (LADDER) database: a model for advancing research, clinical guidance, and therapeutic development for rare conditions.

Angelman syndrome (AS) and duplication 15q (dup15q) syndrome are rare neurogenetic conditions arising from a common locus on the long arm of chromosome 15. Individuals with both conditions share some clinical features (e.g. intellectual disability, epilepsy) and often require lifelong care. Disease-modifying therapies for both conditions are emerging, resulting in a significant need for a better understanding of the natural history of both AS and dup15q. Patient advocacy groups for both conditions recognized a need for a data repository that would link data on individuals from multiple sources to expand research, increase understanding of natural history, and accelerate the development of treatments, resulting in the Linking Angelman and Dup15q Data for Expanded Research (LADDER) Database. This paper describes the development and functionality of the LADDER Database - including challenges, lessons learned, and preliminary feasibility - and how it can be used as a model for other rare conditions.

The LADDER database: a model for advancing research, clinical guidance, and therapeutic development for rare conditions This paper describes the development and functionality of the Linking Angelman and Dup15q Data for Expanded Research (LADDER) Database, which is a data repository for two rare neurogenetic conditions: Angelman syndrome (AS) and duplication 15q (dup15q) syndrome. AS and dup15q syndrome arise from genetic abnormalities on chromosome 15 and share some clinical features (e.g. intellectual disability, epilepsy). LADDER was developed by patient advocacy organizations representing each condition in partnership with RTI International. LADDER links data on individuals from multiple sources to expand research, increase understanding of natural history, and accelerate the development of treatments for both AS and dup15q syndrome. The LADDER Database can be used as a model for expanding research and enhancing clinical trial readiness in other rare conditions.

Latent Class Analysis Identifies Distinctive Behavioral Subtypes in Children with Fragile X Syndrome.

Fragile X syndrome (FXS) is characterized by variable neurobehavioral abnormalities, which leads to difficulties in developing and evaluating treatments and in determining accurate prognosis. We employed a pediatric cross-sectional sample (1,072 males, 338 females) from FORWARD, a clinic-based natural history study, to identify behavioral subtypes by latent class analysis. Input included co-occurring behavioral conditions, sleep and sensory problems, autistic behavior scales (SCQ, SRS-2), and the Aberrant Behavior Checklist revised for FXS (ABCFX). A 5-class solution yielded the most clinically meaningful, pharmacotherapy independent behavioral groups with distinctive SCQ, SRS-2, and ABCFX profiles, and adequate non-overlap (≥ 71%): "Mild" (31%), "Moderate without Social Impairment" (32%), "Moderate with Social Impairment" (7%), "Moderate with Disruptive Behavior" (20%), and "Severe" (9%). Our findings support FXS subtyping, for improving clinical management and therapeutic development.

Patterns and trends in contraceptive use among women attending Title X clinics and a national sample of low-income women.

OBJECTIVES: To describe the types of contraception used by women attending Title X-funded clinics and a comparable group of low-income reproductive-age women at risk of unintended pregnancy. STUDY DESIGN: We estimated the percentage of reproductive aged (15-44 years) women using contraception, by method type and level of effectiveness in preventing pregnancy (i.e., most, moderately, and less effective), using Title X Family Planning Annual Report (2006-2016) and National Survey of Family Growth (2006-2015) data. We divided most effective methods into permanent (female and male sterilization) and reversible (long-acting reversible contraceptives [LARCs]) methods. RESULTS: Among Title X clients during 2006-2016, use of LARCs increased (3-14%); use of moderately effective methods decreased (64-54%); and use of sterilization (~ 2%), less effective methods (21-20%), and no method (8-7%) was unchanged. These same trends in contraceptive use were observed in a comparable group of women nationally during 2006-2015, during which LARC use increased (5-19%, p < .001); moderately effective method use decreased (60-48%, p < .001); and use of sterilization (~5%), less effective methods (19%), and no method (11-10%) was unchanged. CONCLUSIONS: The contraceptive method mix among Title X clients differs from that of low-income women at risk of unintended pregnancy nationally, but general patterns and trends are similar in the two populations. Research is needed to understand whether method use patterns among low-income women reflect their preferences, access, or the conditions of the supply environment. IMPLICATIONS: This study contributes to our understanding of patterns and trends in contraceptive use among two groups of reproductive-age women - Title X clients and low-income women nationally who are at risk of unintended pregnancy. The findings highlight areas for further research.

Trends in Cervical Cancer Screening in Title X-Funded Health Centers - United States, 2005-2015.

Cervical cancer screening is critical to early detection and treatment of precancerous cells and cervical cancer. In 2015, 83% of U.S. women reported being screened per current recommendations, which is below the Healthy People 2020 target of 93% (1,2). Disparities in screening persist for women who are younger (aged 21-30 years), have lower income, are less educated, are uninsured, lack a source of health care, or who self-identify as Asian or American Indian/Alaska Native (2). Women who are never screened or rarely screened are more likely to develop cancer and receive a cancer diagnosis at later stages than women who are screened regularly (3). In 2013, cervical cancer was diagnosed in 11,955 women in the United States, and 4,217 died from the disease (4). Aggregated administrative data from the Title X Family Planning Program were used to calculate the percentage of female clients served in Title X-funded health centers who received a Papanicolaou (Pap) test during 2005-2015. Trends in the percentage of Title X clients screened for cervical cancer were examined in relation to changes in cervical cancer screening guidelines, particularly the 2009 American College of Obstetricians and Gynecologists (ACOG) update that raised the age for starting cervical cancer screening to 21 years (5) and the 2012 alignment of screening guidelines from ACOG, the U.S. Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS) on the starting age (21 years), screening interval (3 or 5 years), and type of screening test (6-8). During 2005-2015, the percentage of female clients screened for cervical cancer dropped continually, with the largest declines occurring in 2010 and 2013, notably a year after major updates to the recommendations. Although aggregated data contribute to understanding of cervical cancer screening trends in Title X centers, studies using client-level and encounter-level data are needed to assess the appropriateness of cervical cancer screening in individual cases.

Do tobacco countermarketing campaigns increase adolescent under-reporting of smoking?

This study assesses whether a national anti-tobacco campaign for youth could create a social context that would elevate social desirability response bias on surveys, as measured by an increase in under-reporting of smoking. This could give rise to data that falsely suggest a campaign-induced decline in youth smoking, or it could exaggerate campaign effects. Data were obtained from a national sample of 5511 students from 48 high schools that were matched to schools sampled for the 2002 National Youth Tobacco Survey (NYTS). Self-reported smoking was compared with biochemical indicators of smoking, measured using saliva cotinine. The rate of under-reporting detected was 1.3%. Level of truth exposure was not related to under-reporting. This study suggests that for high school students, anti-tobacco campaigns are not an important cause of social desirability responses on surveys, and that in general under-reporting smoking is not a major source of error in school-based surveys.

Reactions of young adult smokers to warning labels on cigarette packages.

BACKGROUND: In 1984, the United States Congress enacted legislation requiring four new warning labels for cigarettes; warning labels in the United States have not changed since then. Other countries, such as Canada, have taken a more active and aggressive approach. The purpose of this study was to examine how U.S. smokers and former smokers might respond to stronger and more graphic warnings for U.S. cigarettes packages. METHODS: Data were collected in 2003 and analyzed in 2004. The perceived impact and effectiveness of the more-explicit Canadian labels was examined among young adult smokers (n=572) and former smokers (n=191) between the ages of 18 and 24 years in the United States, using a web-based survey that allowed participants to view both the text-only and the text-plus-graphic warning labels. RESULTS: Both current and former smokers thought that cigarette warning labels with text plus graphics were substantially more of a deterrent than text-only labels. The perceived effectiveness of these labels was not only higher overall, but also for the specific areas of smoking-related health effects, prevention, cessation, and maintenance of abstinence. Few differences were noted by gender. CONCLUSIONS: The findings from this study support previous research that has found that text-plus-graphic warning labels are more salient and potentially more effective than text-only labels.

Progression to established smoking among US youths.

OBJECTIVES: Our study presents national estimates of the proportion of youths in each of 7 stages of smoking and investigates the associations between risk/protective factors and progression to established smoking. METHODS: We analyzed data from the 1999 and 2000 National Youth Tobacco Surveys. RESULTS: In 1999 and 2000, 48.6% of US adolescents had at least experimented with tobacco, and 7.8% were established smokers. Important correlates of progression to established smoking included parental advice not to smoke, antismoking lessons in school, susceptibility to tobacco industry advertising and promotion, peer smoking, and exposure to smoking at home. CONCLUSIONS: Interventions to stop adolescent progression to established smoking should target susceptible never smokers and early experimenters as well as those in later stages of smoking.