Matthew C. Walsh

On the origin of smallpox: Correlating variola phylogenics with historical smallpox records

Human disease likely attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for >2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because VARV has a large, slowly evolving DNA genome, we were able to construct a robust phylogeny of VARV by analyzing concatenated single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. Our results show two primary VARV clades, which likely diverged from an ancestral African rodent-borne variola-like virus either ≈16,000 or ≈68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. Another primary clade included both alastrim minor, a phenotypically mild smallpox described from the American continents, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP, and then further diverged into two subclades at least 800 YBP. All of these analyses indicate that the divergence of alastrim and variola major occurred earlier than previously believed.

Cancer Information Sources Used by Patients to Inform and Influence Treatment Decisions

Previous research has indicated that treatment staff often underestimate the informational needs of cancer patients. In this study, the authors determined the total number of information sources obtained and used to influence treatment decisions, and the clinical and demographic factors associated with the use of specific sources of information in cancer patients. Participants were identified by the statewide cancer registry and diagnosed in 2004 with breast, colorectal, lung, or prostate cancer. A self-administered mailed questionnaire elicited cancer treatments, demographics, and information sources used to make treatment decisions. Of those surveyed, 1,784 (66%) participated and responded to all questions regarding information use. Over 69% of study participants reported obtaining information from a source other than the treatment staff. Significant predictors of using additional information sources included younger age, higher income, higher education, complementary and alternative medicine (CAM) use, and reporting shared decision making (all p values <.01). Participants with a college degree were more likely to use the Internet (OR 3.7; 95% CI 1.5–9.0) and scientific research reports (OR 3.3; 95% CI 1.6–6.9) to influence treatment decisions compared with those without a high school degree. Support group use to influence treatment decisions was not associated with socioeconomic variables but did vary by cancer type and CAM use. The sources of information study participants obtained and used to influence treatment decisions varied strongly by socioeconomic and demographic variables. These findings provide a deeper understanding of the information needs of cancer patients and have implications for dissemination strategies that can minimize disparities in access to cancer information.

Predictors of Family Conflict at the End of Life: The Experience of Spouses and Adult Children of Persons with Lung Cancer

PURPOSE Guided by an explanatory matrix of family conflict at the end of life, the purpose of this article was to examine the correlates and predictors of family conflict reported by 155 spouses and adult children of persons with lung cancer. DESIGN AND METHODS A cross-sectional statewide survey of family members of persons who died from lung cancer was conducted as part of the larger study on the Assessment of Cancer CarE and SatiSfaction in Wisconsin. RESULTS Significant bivariate correlations were found between family conflict and family context variables (i.e., a history of conflict, younger respondent age, race, and specified end-of-life care wishes of the patient), conditions (i.e., greater physical and psychological clinical care needs of the patient), and contributing factors (i.e., communication constraints and family asserting control). In the multivariate model, significant predictors of family conflict included prior family conflict, race, communication constraints, and family members asserting control; the model explained 72% of the variance in conflict. IMPLICATIONS Implications for routine assessment and screening to identify families at risk and recommendations for the development and testing of interventions to facilitate shared decision making and enhance open communication among at-risk families are highlighted.

Reporting of human genome epidemiology (HuGE) association studies: an empirical assessment

BackgroundSeveral thousand human genome epidemiology association studies are published every year investigating the relationship between common genetic variants and diverse phenotypes. Transparent reporting of study methods and results allows readers to better assess the validity of study findings. Here, we document reporting practices of human genome epidemiology studies.MethodsArticles were randomly selected from a continuously updated database of human genome epidemiology association studies to be representative of genetic epidemiology literature. The main analysis evaluated 315 articles published in 2001–2003. For a comparative update, we evaluated 28 more recent articles published in 2006, focusing on issues that were poorly reported in 2001–2003.ResultsDuring both time periods, most studies comprised relatively small study populations and examined one or more genetic variants within a single gene. Articles were inconsistent in reporting the data needed to assess selection bias and the methods used to minimize misclassification (of the genotype, outcome, and environmental exposure) or to identify population stratification. Statistical power, the use of unrelated study participants, and the use of replicate samples were reported more often in articles published during 2006 when compared with the earlier sample.ConclusionWe conclude that many items needed to assess error and bias in human genome epidemiology association studies are not consistently reported. Although some improvements were seen over time, reporting guidelines and online supplemental material may help enhance the transparency of this literature.

COMPLICATED GRIEF SYMPTOMS IN CAREGIVERS OF PERSONS WITH LUNG CANCER: THE ROLE OF FAMILY CONFLICT, INTRAPSYCHIC STRAINS, AND HOSPICE UTILIZATION *

Guided by a stress process conceptual model, this study examines social and psychological determinants of complicated grief symptoms focusing on family conflict, intrapsychic strains, and the potential moderating effect of care quality and hospice utilization. Relying on data from 152 spouse and adult child lung cancer caregiver survey respondents, drawn from an ancillary study of the Assessment of Cancer CarE and SatiSfaction (ACCESS) in Wisconsin, hierarchical multiple regression analysis was used to examine determinants of complicated grief. After controlling for contextual factors and time since death, complicated grief symptoms were higher among caregivers with less education, among families with lower prior conflict but higher conflict at the end-of-life, who had family members who had difficulty accepting the illness, and who were caring for patients with greater fear of death. Additionally, hospice utilization moderated the effect of fear of death on complicated grief. Findings suggest that family conflict, intrapsychic strains, and hospice utilization may help to explain the variability found in complicated grief symptoms among bereaved caregivers. Implications for enhancing complicated grief assessment tools and preventative interventions across the continuum of cancer care are highlighted.

HEALTH LITERACY AND HEALTH-RELATED QUALITY OF LIFE AMONG A POPULATION-BASED SAMPLE OF CANCER PATIENTS

Health-related quality of life is an important outcome in cancer care. A few studies indicate that health literacy influences cancer patients’ health-related quality of life, but additional investigation is needed. The authors examined the relation between health literacy and health-related quality of life among cancer patients. A cross-sectional survey was conducted with cancer patients in Wisconsin during 2006–2007. Data on sociodemographics, clinical characteristics, health-related quality of life, and health literacy were obtained from the states cancer registry and a mailed questionnaire. Regression analyses were used to characterize the association between health-related quality of life and health literacy. The study sample included 1,841 adults, newly diagnosed with lung, breast, colorectal, or prostate cancer in 2004 (response rate = 68%). Health-related quality of life was measured with the Functional Assessment of Cancer Therapy-General. Adjusting for confounders, higher health literacy was associated with greater health-related quality of life (p < .0001). Controlling for covariates, we found significant differences between those in the highest and lowest health literacy categories (p < .0001) and in the physical (p < .0001), functional (p < .0001), emotional (p < .0001), and social (p = .0007) well-being subscales. These associations exceeded the minimally important difference threshold for overall health-related quality of life and functional well-being. Health literacy is positively and independently associated with health-related quality of life among cancer patients. These findings support adoption of health literacy best practices by cancer care systems.

Predictors of discordance between perceived and objective neighborhood data

PURPOSE Pathways by which the social and built environments affect health can be influenced by differences between perception and reality. This discordance is important for understanding health impacts of the built environment. This study examines associations between perceived and objective measures of 12 nonresidential destinations, as well as previously unexplored sociodemographic, lifestyle, neighborhood, and urbanicity predictors of discordance. METHODS Perceived neighborhood data were collected from participants of the Survey of the Health of Wisconsin, using a self-administered questionnaire. Objective data were collected using the Wisconsin Assessment of the Social and Built Environment, an audit-based instrument assessing built environment features around each participants residence. RESULTS Overall, there was relatively high agreement, ranging from 50% for proximity to parks to more than 90% for golf courses. Higher education, positive neighborhood perceptions, and rurality were negatively associated with discordance. Associations between discordance and depression, disease status, and lifestyle factors appeared to be modified by urbanicity level. CONCLUSIONS These data show perceived and objective neighborhood environment data are not interchangeable and the level of discordance is associated with or modified by individual and neighborhood factors, including the level of urbanicity. These results suggest that consideration should be given to including both types of measures in future studies.

A method for statistically comparing spatial distribution maps.

BackgroundEcological niche modeling is a method for estimation of species distributions based on certain ecological parameters. Thus far, empirical determination of significant differences between independently generated distribution maps for a single species (maps which are created through equivalent processes, but with different ecological input parameters), has been challenging.ResultsWe describe a method for comparing model outcomes, which allows a statistical evaluation of whether the strength of prediction and breadth of predicted areas is measurably different between projected distributions. To create ecological niche models for statistical comparison, we utilized GARP (Genetic Algorithm for Rule-Set Production) software to generate ecological niche models of human monkeypox in Africa. We created several models, keeping constant the case location input records for each model but varying the ecological input data. In order to assess the relative importance of each ecological parameter included in the development of the individual predicted distributions, we performed pixel-to-pixel comparisons between model outcomes and calculated the mean difference in pixel scores. We used a two sample Students t-test, (assuming as null hypothesis that both maps were identical to each other regardless of which input parameters were used) to examine whether the mean difference in corresponding pixel scores from one map to another was greater than would be expected by chance alone. We also utilized weighted kappa statistics, frequency distributions, and percent difference to look at the disparities in pixel scores. Multiple independent statistical tests indicated precipitation as the single most important independent ecological parameter in the niche model for human monkeypox disease.ConclusionIn addition to improving our understanding of the natural factors influencing the distribution of human monkeypox disease, such pixel-to-pixel comparison tests afford users the ability to empirically distinguish the significance of each of the diverse environmental parameters included in the modeling process. This method will be particularly useful in situations where the outcomes (maps) appear similar upon visual inspection (as are generated with other modeling programs such as MAXENT), as it allows an investigator the capacity to explore subtle differences among ecological parameters and to demonstrate the individual importance of these factors within an overall model.

The association between neighborhood economic hardship, the retail food environment, fast food intake, and obesity: findings from the Survey of the Health of Wisconsin

BackgroundNeighborhood-level characteristics such as economic hardship and the retail food environment are assumed to be correlated and to influence consumers’ dietary behavior and health status, but few studies have investigated these different relationships comprehensively in a single study. This work aims to investigate the association between neighborhood-level economic hardship, the retail food environment, fast food consumption, and obesity prevalence.MethodsLinking data from the population-based Survey of the Health of Wisconsin (SHOW, n = 1,570, 2008–10) and a commercially available business database, the Wisconsin Retail Food Environment Index (WRFEI) was defined as the mean distance from each participating household to the three closest supermarkets divided by the mean distance to the three closest convenience stores or fast food restaurants. Based on US census data, neighborhood-level economic hardship was defined by the Economic Hardship Index (EHI). Relationships were analyzed using multivariate linear and logistic regression models.ResultsSHOW residents living in neighborhoods with the highest economic hardship faced a less favorable retail food environment (WRFEI = 2.53) than residents from neighborhoods with the lowest economic hardship (WRFEI = 1.77; p-trend < 0.01). We found no consistent or significant associations between the WRFEI and obesity and only a weak borderline-significant association between access to fast food restaurants and self-reported fast food consumption (≥2 times/week, OR = 0.59-0.62, p = 0.05-0.09) in urban residents. Participants reporting higher frequency of fast food consumption (≥2 times vs. <2 times per week) were more likely to be obese (OR = 1.35, p = 0.06).ConclusionThis study indicates that neighborhood-level economic hardship is associated with an unfavorable retail food environment. However inconsistent or non-significant relationships between the retail food environment, fast food consumption, and obesity were observed. More research is needed to enhance methodological approaches to assess the retail food environment and to understand the complex relationship between neighborhood characteristics, health behaviors, and health outcomes.

Oral Health Equity and Unmet Dental Care Needs in a Population-Based Sample: Findings From the Survey of the Health of Wisconsin

OBJECTIVES We used objective oral health screening and survey data to explore individual-, psychosocial-, and community-level predictors of oral health status in a statewide population of adults. METHODS We examined oral health status in a sample of 1453 adult Wisconsin residents who participated in the Survey of the Health of Wisconsin Oral Health Screening project, conducted with the Wisconsin Department of Health Services during 2010. RESULTS We found significant disparities in oral health status across all individual-, psychosocial-, and community-level predictors. More than 15% of participants had untreated cavities, and 20% did not receive needed oral health care. Individuals who self-reported unmet need for dental care were 4 times as likely to have untreated cavities as were those who did not report such a need, after controlling for sociodemographic and behavioral factors. CONCLUSIONS Our results suggested that costs were a primary predictor of access to care and poor oral health status. The results underscored the role that primary care, in conjunction with dental health care providers, could play in promoting oral health care, particularly in reducing barriers (e.g., the costs associated with unmet dental care) and promoting preventive health behaviors (e.g., teeth brushing).