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author:("hereford, A")
1.  Building a Virtual Environment for Diabetes Self-Management Education and Support 
The authors developed an immersive diabetes community to provide diabetes self-management education and support for adults with type 2 diabetes. In this article the authors describe the procedures used to develop this virtual environment (VE). Second Life Impacts Diabetes Education & Self-Management (SLIDES), the VE for our diabetes community was built in Second Life. Social Cognitive Theory, behavioral principles and key aspects of virtual environments related to usability were applied in the development in this VE. Collaboration between researchers, clinicians and information technology (IT) specialists occurred throughout the development process. An interactive community was successfully built and utilized to provide diabetes self-management education and support. VEs for health applications may be innovative and enticing, yet it must be kept in mind that there are substantial effort, expertise, and usability factors that must be considered in the development of these environments for health care consumers.
PMCID: PMC4330567
Diabetes; Diabetes Education; Self-Management; Technical Architecture; Virtual Environment
2.  Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a review of literature 
Patients diagnosed with juvenile-onset systemic lupus erythematosus (JSLE) often have skin and oral lesions as part of their presentation. These mucocutaneous lesions, as defined by the American College of Rheumatology (ACR) in 1997, include malar rash, discoid rash, photosensitivity and oral ulcers. It is therefore essential to recognize mucocutaneous lesions to accurately diagnose JSLE. The mucocutaneous lesions can be divided into those with classical histological features (LE specific) and those strongly associated with and forming part of the diagnostic spectrum, but without the classical histological changes of lupus (LE nonspecific). A malar rash is the most commonly associated LE specific dermatological presentation. This skin manifestation is an acute form and also correlates with disease activity. Subacute (polycyclic or papulosquamous lesions) and chronic (discoid lesions) forms, whilst showing classical histological changes supportive of lupus, are less commonly associated with systemic lupus and do not correlate with disease activity. The most commonly associated skin lesions without classical lupus changes are cutaneous vasculitis, oral ulcers and diffuse non-scarring alopecia. These signs frequently relate to disease activity. An understanding of cutaneous signs and symptoms of lupus in children is important to avoid delay in diagnosis. They will often improve as lupus is adequately controlled and their reappearance is often the first indicator of a disease flare.
PMCID: PMC4292833  PMID: 25587243
Juvenile-onset systemic lupus erythematosus; Mucocutaneous lupus lesions; Lupus erythematosus specific lesions; Lupus erythematosus nonspecific lesions; Diagnosis; Treatment
3.  Increases in physical activity may affect quality of life differently in men and women: The PACE project 
Obesity is associated with impaired quality of life (QoL), but less is known about physical activity. We investigated how decreases in body mass index (BMI) and increases in activity affect obesity-specific QoL and potential gender differences in associations.
In a large worksite-randomized trial of a multilevel intervention on diet and physical activity behaviors, we conducted a cohort analysis at two years of follow-up. Self-reported activity and Obesity and Weight-Loss Quality Of Life (OWLQOL) were analyzed for individual-level associations using linear mixed models accounting for random worksite effects.
Gender modified the BMI-OWLQOL relationship, so analyses were conducted for males and females separately. Adjusting for demographic confounders, baseline OWLQOL, and several worksite-level variables including intervention arm, a 1.9 unit decrease in BMI (the interquartile range) was associated with an OWLQOL increase of 1.7 (95% CI: 1.2, 2.2) in males and 3.6 (95% CI: 3.2, 4.0) in females. Similarly, a 23 unit increase in physical activity score was associated with an OWLQOL increase of 0.9 (95% CI: 0.5, 1.4) in males and 1.6 (95% CI: 1.0, 2.3) in females. Physical activity associations were attenuated when adjusting for change in BMI, but remained significant for women (mean BMI 27.8 kg/m2).
This is the first study to demonstrate that increasing physical activity may improve obesity-specific QoL to a greater extent in women, particularly among overweight women, independent of BMI. Results may inform the design of interventions tailored to women targeting well-being through messages of increasing physical activity.
PMCID: PMC3760977  PMID: 23504523
Body mass index; physical activity; quality of life; weight loss; women
4.  Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling 
Nature genetics  2014;46(5):503-509.
The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer a gain-of-function - so that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.
PMCID: PMC4004585  PMID: 24686847
5.  The Women’s Health Initiative Hormone Therapy Trials: Update and Overview of Health Outcomes During the Intervention and Post-Stopping Phases 
Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.
To provide a comprehensive, integrated overview of findings from the two Women’s Health Initiative (WHI) hormone therapy (HT) trials with extended post-intervention follow up.
27,347 postmenopausal women, age 50–79 years, were enrolled at 40 US centers. Interventions were conjugated equine estrogens (CEE, 0.625 mg/day) with medroxyprogesterone acetate (MPA, 2.5 mg/day) for women with an intact uterus (N = 16,608) and CEE alone for women with hysterectomy (N= 10,739), or their placebos. Intervention continued for 5.6 and 7.2 years (median), respectively, with cumulative follow-up of 13 years through September 30, 2010.
The primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and deaths. Secondary and quality-of-life outcomes were also assessed.
During the intervention phase for CEE+MPA, the hazard ratio (HR) for CHD was 1.18 (95% confidence interval [CI] 0.95–1.45) and overall risks outweighed benefits, with increases in invasive breast cancer, stroke, pulmonary embolism, and the global index. Other risks included increased dementia (in women >65 years), gallbladder disease, and urinary incontinence, while benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Post-intervention, most risks and benefits dissipated, although some elevation in breast cancer risk persisted (cumulative hazard ratio [HR] =1.28; 95% confidence interval, 1.11–1.48). During intervention for CEE alone, risks and benefits were more balanced, with a HR for CHD of 0.94 (0.78–1.14), increased stroke and venous thrombosis, decreased hip fractures and diabetes, and over cumulative follow-up, decreased breast cancer (HR=0.79 [0.65–0.97]). Neither regimen affected all-cause mortality. With CEE, younger women (50–59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P values for trend by age <0.05), but not for stroke and venous thrombosis. Absolute risks of adverse events (measured by the global index) per 10,000 women per year on CEE+MPA ranged from 12 excess cases for age 50–59 to 38 for age 70–79 and, for CEE, from 19 fewer cases for age 50–59 to 51 excess cases for age 70–79. Results for quality of life outcomes in both trials were mixed.
Menopausal hormone therapy has a complex pattern of risks and benefits. While appropriate for symptom management in some women, its use for chronic disease prevention is not supported by the WHI randomized trials.
clinical Identifier: NCT00000611
PMCID: PMC3963523  PMID: 24084921
6.  Psychological Distress, Social Withdrawal, and Coping Following Receipt of an Abnormal Mammogram Among Different Ethnicities: A Mediation Model 
Oncology nursing forum  2014;41(5):523-532.
To explore ethnic differences in psychological distress and social withdrawal after receiving an abnormal mammogram result and to assess if coping strategies mediate ethnic differences.
Descriptive correlational.
Two urban mobile mammography units and a rural community hospital in the state of Washington.
41 Latina and 41 non-Latina Caucasian (NLC) women who had received an abnormal mammogram result.
Women completed standard sociodemographic questions, Impact of Event Scale–Revised, the social dimension of the Psychological Consequences Questionnaire, and the Brief COPE.
Main Research Variables
Ethnicity, psychological distress, social withdrawal, and coping.
Latinas experienced greater psychological distress and social withdrawal compared to NLC counterparts. Denial as a coping strategy mediated ethnic differences in psychological distress. Religious coping mediated ethnic differences in social withdrawal.
Larger population-based studies are necessary to understand how ethnic differences in coping strategies can influence psychological outcomes. This is an important finding that warrants additional study among women who are and are not diagnosed with breast cancer following an abnormal mammogram.
Implications for Nursing
Nurses may be able to work with Latina patients to diminish denial coping and consequent distress. Nurses may be particularly effective, given cultural values concerning strong interpersonal relationships and respect for authority figures.
PMCID: PMC4172284  PMID: 25158657
breast cancer; coping; cultural competence; Hispanic; prevention; detection; quality of life
20.  Adherence to WCRF/AICR cancer prevention recommendations and risk of post-menopausal breast cancer 
In 2007 the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) released eight recommendations related to body fatness, physical activity and diet aimed at preventing the most common cancers worldwide. However, limited information exists on the association between meeting these recommendations and risks of specific cancers, including breast cancer.
We operationalized six recommendations (related to body fatness, physical activity, foods that promote weight gain, plant foods, red and processed meats, and alcohol) and examined their association with invasive breast cancer incidence over 6.7 years of follow-up in the VITamins And Lifestyle (VITAL) study cohort. Participants included 30,797 post-menopausal women ages 50–76 years at baseline in 2000–2002 with no history of breast cancer. Breast cancers (n=899) were tracked through the Western Washington Surveillance, Epidemiology and End Results (SEER) database.
Breast cancer risk was reduced by 60% in women who met at least five recommendations compared to those who met none (HR: 0.40; 95% CI: 0.25–0.65; Ptrend<0.001). Further analyses that sequentially removed individual recommendations least associated with reduced risk suggested that this reduction is due to meeting recommendations related to body fatness, plant foods and alcohol (HR for meeting vs. not meeting these three recommendations: 0.38; 95% CI: 0.25–0.58; Ptrend <0.001).
Meeting the WCRF/AICR cancer prevention recommendations, specifically those related to alcohol, body fatness and plant foods, is associated with reduced post-menopausal breast cancer incidence.
Increased adherence to the WCRF/AICR cancer prevention recommendations could substantially reduce post-menopausal breast cancer risk in US women.
PMCID: PMC3774119  PMID: 23780838
cancer prevention; breast cancer; recommendations; diet; alcohol
21.  Healthcare Utilization in Medical Intensive Care Unit Survivors with Alcohol Withdrawal 
Rehospitalization is an important and costly outcome that occurs commonly in several diseases encountered in the medical intensive care unit (ICU). Although alcohol use disorders are present in 40% of ICU survivors and alcohol withdrawal is the most common alcohol-related reason for admission to an ICU, rates and predictors of rehospitalization have not been previously reported in this population.
We conducted a retrospective cohort study of medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal using two administrative databases. The primary outcome was time to rehospitalization or death. Secondary outcomes included time to first emergency department or urgent care clinic visit in the subset of ICU survivors who were not rehospitalized. Cox proportional hazard models were adjusted for age, gender, race, homelessness, smoking, and payer source.
Of 1,178 patients discharged from the medical ICU over the study period, 468 (40%) were readmitted to the hospital and 54 (4%) died within 1 year. Schizophrenia (HR 2.23, 95% CI 1.57, 3.34, p < 0.001), anxiety disorder (HR 2.04, 95% CI 1.30, 3.32, p < 0.01), depression (HR 1.62, 95% CI 1.05, 2.40, p = 0.03), and Deyo comorbidity score ≥ 3 (HR 1.43, 95% CI 1.09, 1.1.89, p = 0.01) were significant predictors of time to death or first rehospitalization. Bipolar disorder was associated with time to first emergency department or urgent care clinic visit (HR 2.03, 95% CI 1.24, 3.62, p < 0.01) in the 656 patients who were alive and not rehospitalized within one year.
The presence of a psychiatric comorbidity is a significant predictor of multiple measures of unplanned healthcare utilization in medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal. This finding highlights the potential importance of targeting longitudinal multidisciplinary care to patients with a dual diagnosis.
PMCID: PMC4045620  PMID: 23647435
alcohol withdrawal; alcohol use disorder; intensive care unit; rehospitalization; dual diagnosis
22.  Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: Results from a crossover trial 
By increasing blood folate concentrations, folic acid supplementation reduces risk for neural tube defect-affected pregnancies, and lowers homocysteine concentrations. We assessed response of red blood cell (RBC) and serum folate to folic acid supplementation, and examined association of response with the genetic polymorphism C677T of the methylenetetrahydrofolate NAD(P)H (MTHFR) gene.
Methods and Results
Randomized, controlled, crossover trial with two folic acid supplement treatment periods and a 30-week washout period. The primary outcome is blood folate (serum and RBC) concentrations. Volunteers (n=142) aged 18-69 were randomized to two of three doses (0, 200, and 400 μg) of folic acid for twelve weeks. Serum folate response depended on treatment period with significant responses to 200 μg seen only in the second treatment periods (4.4 ng/mL or 3.4 ng/mL). Additionally, serum folate increased as folic acid dose increased to 400 μg (p< 0.01) and response was greater after the washout period (8.7 ng/mL), than after a 6-week run-in (2.3 ng/mL). The differential change attributable to a daily supplement of 400 μg compared to 200 μg was 96.8 ng/mL; while the change attributable to 400 μg compared to 0 μg was 121.4. Increases in RBC folate concentrations with 400 μg occurred within MTHFR gene mutation (C677T); and in the African American group.
Serum folate concentration is responsive to modest increases in folic acid intake. Red blood cell folate increases only with higher additional doses of folic acid supplementation, and this is true for each MTHFR C677T genotype.
PMCID: PMC4132693  PMID: 23456769
Folic acid; fortification; methylenetetrahydrofolate reductase; supplementation
23.  Changes in Physical Activity and Body Composition in Postmenopausal Women over Time 
Higher physical activity (PA) has been associated with greater attenuation of body-fat gain and preservation of lean mass across the lifespan. These analyses aimed to determine relationships of change in PA to changes in fat and lean body mass in a longitudinal prospective study of postmenopausal women.
Among 11,491 women enrolled at three Women’s Health Initiative (WHI) clinical centers were selected to undergo dual-energy x-ray absorptiometry (DXA), 8,352 had baseline body composition measurements, with at least one repeated measure at yr 1, 3, and 6. PA data were obtained by self-report at baseline, 3 and 6 yr of follow-up. Time-varying PA impact on change in lean and fat mass during the six-yr study period for age groups (50–59y, 60–69y, 70–79y) was estimated using mixed effects linear regression.
Baseline PA and body composition differed significantly among the three age groups. The association of change in fat mass from baseline and time-varying PA differed across the three age groups (p=0.0006). In women aged 50–59, gain in fat mass from baseline was attenuated with higher levels of physical activity. Women aged 70–79 lost fat mass at all PA levels. In contrast, change in lean mass from baseline and time-varying PA did not differ by age group (p=0.1935).
The association between PA and change in fat mass varies by age group, with younger, but not older, women benefitting from higher levels of aerobic PA. Higher levels of aerobic activity are not associated with changes in lean mass, which tends to decrease in older women regardless of activity level. Greater attention to resistance training exercises may be needed to prevent lean mass loss as women age.
PMCID: PMC3715578  PMID: 23439422
lean mass changes; exercise; aging; women; sarcopenia
24.  Recent physical activity in relation to DNA damage and repair using the comet assay 
Limited evidence suggests that very high-intensity exercise is positively associated with DNA damage but moderate exercise may be associated with DNA repair.
Participants were 220 healthy, Washington State 50–76 year-olds in the validity/biomarker sub-study of the VITamins And Lifestyle (VITAL) cohort, who provided blood samples and completed questionnaires assessing recent physical activity and demographic and health factors. Measures included nested activity subsets: total activity, moderate- plus high-intensity activity, and high-intensity activity. DNA damage (n=122) and repair (n=99) were measured using the comet assay. Multivariate linear regression was used to estimate regression coefficients and associated 95% confidence intervals (CIs) for relationships between MET-hours per week of activity and each DNA outcome (damage, and 15- and 60-minute repair capacities).
DNA damage was not associated with any measure of activity. However, 60-minute DNA repair was positively associated with both total activity (β=0.21, 95% CI: 0.0057, 0.412; p=0.044) and high-intensity activity (β=0.31, 95% CI: 0.20, 0.60; p=0.036), adjusting for age, sex, BMI, and current multivitamin use.
This study is the first to assess broad ranges of activity intensity levels related to DNA damage and repair. Physical activity was unrelated to DNA damage but was associated with increased repair.
PMCID: PMC3844056  PMID: 23574930
Exercise; Body Mass Index; cancer prevention
25.  Developing a provisional, international Minimal Dataset for Juvenile Dermatomyositis: for use in clinical practice to inform research 
Juvenile dermatomyositis (JDM) is a rare but severe autoimmune inflammatory myositis of childhood. International collaboration is essential in order to undertake clinical trials, understand the disease and improve long-term outcome. The aim of this study was to propose from existing collaborative initiatives a preliminary minimal dataset for JDM. This will form the basis of the future development of an international consensus-approved minimum core dataset to be used both in clinical care and inform research, allowing integration of data between centres.
A working group of internationally-representative JDM experts was formed to develop a provisional minimal dataset. Clinical and laboratory variables contained within current national and international collaborative databases of patients with idiopathic inflammatory myopathies were scrutinised. Judgements were informed by published literature and a more detailed analysis of the Juvenile Dermatomyositis Cohort Biomarker Study and Repository, UK and Ireland.
A provisional minimal JDM dataset has been produced, with an associated glossary of definitions. The provisional minimal dataset will request information at time of patient diagnosis and during on-going prospective follow up. At time of patient diagnosis, information will be requested on patient demographics, diagnostic criteria and treatments given prior to diagnosis. During on-going prospective follow-up, variables will include the presence of active muscle or skin disease, major organ involvement or constitutional symptoms, investigations, treatment, physician global assessments and patient reported outcome measures.
An internationally agreed minimal dataset has the potential to significantly enhance collaboration, allow effective communication between groups, provide a minimal standard of care and enable analysis of the largest possible number of JDM patients to provide a greater understanding of this disease. This preliminary dataset can now be developed into a consensus-approved minimum core dataset and tested in a wider setting with the aim of achieving international agreement.
PMCID: PMC4113599  PMID: 25075205
Juvenile dermatomyositis; Idiopathic Inflammatory myopathy; International; Collaboration; Dataset; Core set; Disease activity

Results 1-25 (195)