Does genetic testing offer utility as a supplement to traditional family health history intake for inherited disease risk?

CONTENT: This study examines the potential utility of genetic testing as a supplement to family health history to screen for increased risk of inherited disease. Medical conditions are often misreported or misunderstood, especially those related to different forms of cardiac disease (arrhythmias vs. structural heart disease vs. coronary artery disease), female organ cancers (uterine vs. ovarian vs. cervical), and type of cancer (differentiating primary cancer from metastases to other organs). While these nuances appear subtle, they can dramatically alter medical management. For example, different types of cardiac failure (structural, arrhythmia, and coronary artery disease) have inherited forms that are managed with vastly different approaches. METHODS: Using a dataset of over 6,200 individuals who underwent genetic screening, we compared the ability of genetic testing and traditional family health history to identify increased risk of inherited disease. A further, in-depth qualitative study of individuals for whom risk identified through each method was discordant, explored whether this discordance could be addressed through changes in family health history intake. FINDINGS: Of 90 individuals for whom genetic testing indicated significant increased risk for inherited disease, two-thirds (66%) had no corroborating family health history. Specifically, we identify cardiomyopathy, arrhythmia, and malignant hyperthermia as conditions for which discordance between genetic testing and traditional family health history was greatest, and familial hypercholesterolaemia, Lynch syndrome, and hereditary breast and ovarian cancer as conditions for which greater concordance existed. CONCLUSION: We conclude that genetic testing offers utility as a supplement to traditional family health history intake over certain conditions.

Community-Based Participatory Research and its Potential Role in Supporting Diversity in Genomic Science.

OBJECTIVES: This paper seeks to understand why targeted efforts to recruit subjects from underrepresented communities have failed to meaningfully increase diversity of genomic reference data. APPROACH: We review a variety of mechanisms that have attempted to establish trust with communities underrepresented in genomic research, including sophisticated informed consent, broad consent, community consultation, and initiatives designed to diversify the scientific workforce. We also analyze the ability of deep community engagement of the type advanced by community-based participatory research (CBPR) to address deficiencies in previous strategies to build trust. CONCLUSION AND RECOMMENDATION: Previous strategies to build trust do not fully address key concerns related to the foundational aims and projects of scientific inquiry. The techniques of CBPR are well suited to address these concerns and thus build trust. Community engagement strategies show tremendous promise in supporting participation of underrepresented communities in genomic research.

Addressing perceived economic obstacles to genetic testing as a way to mitigate disparities in family health history for adoptees.

In this paper, we ask whether or not we can afford to realize the potential benefits of genetic testing as a screening tool for adoptees. Our method is to provide reasonable cost and savings estimates. We argue that the prospect of cost neutrality should be sufficient to explore the targeted screening for a population who will otherwise suffer an avoidable health disparity in access to inherited disease information. Our goal here is to establish that the investment needed to attain these benefits is not beyond our means.

Geographic variation and risk factors for teenage pregnancy in Uganda.

BACKGROUND: Teenage pregnancy is a global health issue with high rates in sub-Saharan Africa. In Uganda, teenage pregnancy is a public and community health issue. OBJECTIVES: This study hypothesized that there would be regional variations in rates, risk factors and trends of teenage pregnancy in Uganda. METHODS: Data were analyzed from the Uganda Demographic and Health Surveys (UDHS) in 2006 and 2011. The outcome of interest was current pregnancy for females 15 to 19 years of age at the time of the survey. Bivariate analysis was performed for each year to examine the rate and trends of pregnancy by various demographic characteristics. Logistic regression was conducted to assess the association between teenage pregnancy and sociodemographic variables. RESULTS: Uganda's rate of teenage pregnancy increased from 7.3/1000 in 2006 to 8.1/1000 in 2011. The East Central region consistently had the highest rates than other regions. In 2006, teenage pregnancy was significantly associated with being married, living with a partner or separated, as compared to those who were single. Marital and wealth status were also significant predictors of teenage pregnancy based on the 2011 survey. CONCLUSION: The rate of teenage pregnancy in Uganda is high and the trend demonstrated regional variation. Future interventions could focus on regions with high poverty and low education.

The value of genetic testing for family health history of adopted persons.

Lack of family health history experienced by most adopted persons can represent a marked disadvantage. This Comment discusses the role of genetic testing in filling this informational gap and the challenges that need to be overcome.

Does Lack of "Genetic-Relative Family Health History" Represent a Potentially Avoidable Health Disparity for Adoptees?

Many adoptees face a number of challenges relating to separation from biological parents during the adoption process, including issues concerning identity, intimacy, attachment, and trust, as well as (for older adopted children) language and other cultural challenges. One common health challenge faced by adoptees involves lack of access to genetic-relative family health history (GRFHx). Lack of GRFHx represents a disadvantage due to a reduced capacity to identify diseases and recommend appropriate screening for conditions for which the adopted person may be at increased risk. In this article, we draw out common features of traditionally understood "health disparities" in order to identify analogous features in the context of adoptees' lack of GRFHx.

Effect and cost of an after-school dance programme on the physical activity of 11-12 year old girls: The Bristol Girls Dance Project, a school-based cluster randomised controlled trial.

BACKGROUND: The aim of this study was to examine the effectiveness and cost of an after-school dance intervention at increasing the physical activity levels of Year 7 girls (age 11-12). METHODS: A cluster randomised controlled trial was conducted in 18 secondary schools. Participants were Year 7 girls attending a study school. The Bristol Girls Dance Project (BGDP) intervention consisted of up to forty, 75-minute dance sessions delivered in the period immediately after school by experienced dance instructors over 20-weeks. The pre-specified primary outcome was accelerometer assessed mean minutes of weekday moderate to vigorous physical activity (MVPA) at time 2 (52 weeks are T0 baseline assessments). Secondary outcomes included accelerometer assessed mean minutes of weekday MVPA at time 1 (while the intervention was still running) and psychosocial outcomes. Intervention costs were assessed. RESULTS: 571 girls participated. Valid accelerometer data were collected from 549 girls at baseline with 508 girls providing valid accelerometer data at baseline and time 2. There were no differences between the intervention and control group for accelerometer assessed physical activity at either time 1 or time 2. Only one third of the girls in the intervention arm met the pre-set adherence criteria of attending two thirds of the dance sessions that were available to them. Instrumental variable regression analyses using complier average causal effects provided no evidence of a difference between girls who attended the sessions and the control group. The average cost of the intervention was £73 per girl, which was reduced to £63 when dance instructor travel expenses were excluded. CONCLUSION: This trial showed no evidence that an after-school dance programme can increase the physical activity of Year 7 girls. The trial highlighted the difficulty encountered in maintaining attendance in physical activity programmes delivered in secondary schools. There is a need to find new ways to help adolescent girls to be physically active via identifying ways to support and encourage sustained engagement in physical activity over the life course. TRIAL REGISTRATION: ISRCTN52882523.

Toxicity of Pb-contaminated soil to Japanese quail (Coturnix japonica) and the use of the blood-dietary Pb slope in risk assessment.

This study relates tissue concentrations and toxic effects of Pb in Japanese quail (Coturnix japonica) to the dietary exposure of soil-borne Pb associated with mining and smelting. From 0% to 12% contaminated soil, by weight, was added to 5 experimental diets (0.12 to 382 mg Pb/kg, dry wt) and fed to the quail for 6 weeks. Benchmark doses associated with a 50% reduction in delta-aminolevulinic acid dehydratase activity were 0.62 mg Pb/kg in the blood, dry wt, and 27 mg Pb/kg in the diet. Benchmark doses associated with a 20% increase in the concentration of erythrocyte protoporphyrin were 2.7 mg Pb/kg in the blood and 152 mg Pb/kg in the diet. The quail showed no other signs of toxicity (histopathological lesions, alterations in plasma-testosterone concentration, and body and organ weights). The relation of the blood Pb concentration to the soil Pb concentration was linear, with a slope of 0.013 mg Pb/kg of blood (dry wt) divided by mg Pb/kg of diet. We suggest that this slope is potentially useful in ecological risk assessments on birds in the same way that the intake slope factor is an important parameter in risk assessments of children exposed to Pb. The slope may also be used in a tissue-residue approach as an additional line of evidence in ecological risk assessment, supplementary to an estimate of hazard based on dietary toxicity reference values.

Immunological and reproductive health assessment in herring gulls and black-crowned night herons in the Hudson-Raritan Estuary.

Previous studies have shown inexplicable declines in breeding waterbirds within western New York/New Jersey Harbor between 1996 and 2002 and elevated polychlorinated dibenzo-p-dioxins and polychlorinated biphenyls (PCBs) in double-crested cormorant (Phalacrocorax auritus) eggs. The present study assessed associations between immune function, prefledgling survival, and selected organochlorine compounds and metals in herring gulls (Larus argentatus) and black-crowned night herons (Nycticorax nycticorax) in lower New York Harbor during 2003. In pipping gull embryos, lymphoid cells were counted in the thymus and bursa of Fabricius (sites of T and B lymphocyte maturation, respectively). The phytohemagglutinin (PHA) skin response assessed T cell function in gull and heron chicks. Lymphocyte proliferation was measured in vitro in adult and prefledgling gulls. Reference data came from the Great Lakes and Bay of Fundy. Survival of prefledgling gulls was poor, with only 0.68 and 0.5 chicks per nest surviving to three and four weeks after hatch, respectively. Developing lymphoid cells were reduced 51% in the thymus and 42% in the bursa of gull embryos from New York Harbor. In vitro lymphocyte assays demonstrated reduced spontaneous proliferation, reduced T cell mitogen-induced proliferation, and increased B cell mitogen-induced proliferation in gull chicks from New York Harbor. The PHA skin response was suppressed 70 to 80% in gull and heron chicks. Strong negative correlations (r = -0.95 to -0.98) between the PHA response and dioxins and PCBs in gull livers was strong evidence suggesting that these chemicals contribute significantly to immunosuppression in New York Harbor waterbirds.

Expanding Bioshield: a call for caution.

The Bioshield Initiative seeks to stimulate development of new drugs and vaccines to prevent and treat diseases caused by biological agents likely to be used by terrorists, and recent proposals have sought to expand patent protections in this context. To the extent that patent protections are needed as part of the incentive structure for new drug and vaccine development, it may be better to strengthen patent protections on nonterror-related drugs and vaccines to avoid production capacity problems, as well as follow-up research and development problems. However, at the same time, both practical and ethical considerations argue that the good that might be achieved through expanded patent protections come at costs that make this strategy unacceptable.

Access to hospitals in the wake of terrorism: challenges and needs for maintaining public confidence.

The problem of surge capacity in the wake of a terror-related emergency has lead to a number of interesting proposals designed to mitigate the effects of crowds as well as deficiencies in patient care capacities. The most controversial of these is a proposal to close hospital doors in the wake of a mass casualty terror event. However, several specific challenges posed by mass casualty events make closing hospitals doors undesirable. These include the need for efficient movement of resources, maintenance of social order, and providing the moral reassurance needed by the general public in times of crisis. Importantly, these challenges are related to features of terrorist events that distinguish such events from circumstances of "normal" surge that might result in, for example, closure of emergency rooms.

Funding agendas: has bioterror defense been over-prioritized?

Post-9/11, concern about bioterrorism has transformed public health from unappreciated to a central component of national security. Within the War on Terror, bioterrorism preparedness has taken a back seat only to direct military action in terms of funding. Domestically, homelessness, joblessness, crime, education, and race relations are just a few of a litany of pressing issues requiring government attention. Even within the biomedical sciences and healthcare, issues surrounding the fact that more than 40 million Americans lack health insurance, the rising cost of prescription medications, and the use of government funds for research using embryonic stem cells remain unresolved. Should we prioritize a hypothetical threat (bioterrorism), or existing conditions that have implications for identifiable individuals? Even more fundamentally, should we prioritize research aimed at defense from bioterrorism (or even terrorism in general) when there are so many pressing social problems that affect the U.S. population?

Should smallpox vaccine be made available to the general public?

In June 2002, the Advisory Committee on Immunization Practices (ACIP) approved draft recommendations concerning preparation for potential biological terror attacks that utilize the smallpox virus. ACIP recommends against both mandatory and voluntary vaccination of the general public. The present paper examines the moral and political considerations both for and against each of the general public vaccination options considered by the ACIP in the context of the state's authority over vaccination for the purposes of protecting public health. Although it is clear that compulsory mass vaccination is not justified at this time, the issues surrounding voluntary vaccination are more complex. Should smallpox vaccination prior to an outbreak be made available to the general public? The paper concludes that the vaccine should not be made available at this time. This conclusion, however, is based upon contingent features of current circumstances, which would change once an outbreak occurred. In the even of a terror-related outbreak of smallpox, the general public's access to voluntary vaccination would become justified, even in areas beyond where the outbreak has occurred.