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Leveraging Epidemiologic and Clinical Collections for Genomic Studies of Complex Traits.
Crawford DC, Goodloe R, Farber-Eger E, Boston J, Pendergrass SA, Haines JL, Ritchie MD, Bush WS
(2015) Hum Hered 79: 137-46
MeSH Terms: Adult, African Americans, Child, Demography, Female, Gene-Environment Interaction, Genomics, Hispanic Americans, Humans, Male, Nutrition Surveys, Quantitative Trait, Heritable
Show Abstract · Added May 5, 2017
BACKGROUND/AIMS - Present-day limited resources demand DNA and phenotyping alternatives to the traditional prospective population-based epidemiologic collections.
METHODS - To accelerate genomic discovery with an emphasis on diverse populations, we--as part of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study--accessed all non-European American samples (n = 15,863) available in BioVU, the Vanderbilt University biorepository linked to de-identified electronic medical records, for genomic studies as part of the larger Population Architecture using Genomics and Epidemiology (PAGE) I study. Given previous studies have cautioned against the secondary use of clinically collected data compared with epidemiologically collected data, we present here a characterization of EAGLE BioVU, including the billing and diagnostic (ICD-9) code distributions for adult and pediatric patients as well as comparisons made for select health metrics (body mass index, glucose, HbA1c, HDL-C, LDL-C, and triglycerides) with the population-based National Health and Nutrition Examination Surveys (NHANES) linked to DNA samples (NHANES III, n = 7,159; NHANES 1999-2002, n = 7,839).
RESULTS - Overall, the distributions of billing and diagnostic codes suggest this clinical sample is a mixture of healthy and sick patients like that expected for a contemporary American population.
CONCLUSION - Little bias is observed among health metrics, suggesting this clinical collection is suitable for genomic studies along with traditional epidemiologic cohorts.
2015 S. Karger AG, Basel.
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12 MeSH Terms
R-U policy frontiers for health data de-identification.
Xia W, Heatherly R, Ding X, Li J, Malin BA
(2015) J Am Med Inform Assoc 22: 1029-41
MeSH Terms: Algorithms, Computer Security, Confidentiality, Datasets as Topic, Demography, Health Insurance Portability and Accountability Act, Humans, United States
Show Abstract · Added April 10, 2018
OBJECTIVE - The Health Insurance Portability and Accountability Act Privacy Rule enables healthcare organizations to share de-identified data via two routes. They can either 1) show re-identification risk is small (e.g., via a formal model, such as k-anonymity) with respect to an anticipated recipient or 2) apply a rule-based policy (i.e., Safe Harbor) that enumerates attributes to be altered (e.g., dates to years). The latter is often invoked because it is interpretable, but it fails to tailor protections to the capabilities of the recipient. The paper shows rule-based policies can be mapped to a utility (U) and re-identification risk (R) space, which can be searched for a collection, or frontier, of policies that systematically trade off between these goals.
METHODS - We extend an algorithm to efficiently compose an R-U frontier using a lattice of policy options. Risk is proportional to the number of patients to which a record corresponds, while utility is proportional to similarity of the original and de-identified distribution. We allow our method to search 20 000 rule-based policies (out of 2(700)) and compare the resulting frontier with k-anonymous solutions and Safe Harbor using the demographics of 10 U.S. states.
RESULTS - The results demonstrate the rule-based frontier 1) consists, on average, of 5000 policies, 2% of which enable better utility with less risk than Safe Harbor and 2) the policies cover a broader spectrum of utility and risk than k-anonymity frontiers.
CONCLUSIONS - R-U frontiers of de-identification policies can be discovered efficiently, allowing healthcare organizations to tailor protections to anticipated needs and trustworthiness of recipients.
© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Population-level scale-up of cervical cancer prevention services in a low-resource setting: development, implementation, and evaluation of the cervical cancer prevention program in Zambia.
Parham GP, Mwanahamuntu MH, Kapambwe S, Muwonge R, Bateman AC, Blevins M, Chibwesha CJ, Pfaendler KS, Mudenda V, Shibemba AL, Chisele S, Mkumba G, Vwalika B, Hicks ML, Vermund SH, Chi BH, Stringer JS, Sankaranarayanan R, Sahasrabuddhe VV
(2015) PLoS One 10: e0122169
MeSH Terms: Acetic Acid, Adult, Cervical Intraepithelial Neoplasia, Cryotherapy, Delivery of Health Care, Demography, Early Detection of Cancer, Female, HIV Infections, Humans, Mass Screening, Middle Aged, Program Development, Program Evaluation, Uterine Cervical Neoplasms, Zambia
Show Abstract · Added May 13, 2015
BACKGROUND - Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries.
METHODS - In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts.
FINDINGS - Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25-49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women.
INTERPRETATION - We creatively disrupted the 'no screening' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps.
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16 MeSH Terms
Prospective evaluation of the association of nut/peanut consumption with total and cause-specific mortality.
Luu HN, Blot WJ, Xiang YB, Cai H, Hargreaves MK, Li H, Yang G, Signorello L, Gao YT, Zheng W, Shu XO
(2015) JAMA Intern Med 175: 755-66
MeSH Terms: Adult, Aged, Arachis, China, Cohort Studies, Demography, Eating, Feeding Behavior, Female, Humans, Male, Middle Aged, Mortality, Myocardial Ischemia, Nuts, Prospective Studies, Socioeconomic Factors, Southeastern United States, Stroke, Surveys and Questionnaires
Show Abstract · Added March 4, 2015
IMPORTANCE - High intake of nuts has been linked to a reduced risk of mortality. Previous studies, however, were primarily conducted among people of European descent, particularly those of high socioeconomic status.
OBJECTIVE - To examine the association of nut consumption with total and cause-specific mortality in Americans of African and European descent who were predominantly of low socioeconomic status (SES) and in Chinese individuals in Shanghai, China.
DESIGN, SETTING, AND PARTICIPANTS - Three large cohorts were evaluated in the study. One included 71 764 US residents of African and European descent, primarily of low SES, who were participants in the Southern Community Cohort Study (SCCS) in the southeastern United States (March 2002 to September 2009), and the other 2 cohorts included 134 265 participants in the Shanghai Women's Health Study (SWHS) (December 1996 to May 2000) and the Shanghai Men's Health Study (SMHS) (January 2002 to September 2006) in Shanghai, China. Self-reported nut consumption in the SCCS (approximately 50% were peanuts) and peanut-only consumption in the SMHS/SWHS were assessed using validated food frequency questionnaires.
MAIN OUTCOMES AND MEASURES - Deaths were ascertained through linkage with the National Death Index and Social Security Administration mortality files in the SCCS and annual linkage with the Shanghai Vital Statistics Registry and by biennial home visits in the SWHS/SMHS. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs.
RESULTS - With a median follow-up of 5.4 years in the SCCS, 6.5 years in the SMHS, and 12.2 years in the SWHS, 14,440 deaths were identified. More than half of the women in the SCCS were ever smokers compared with only 2.8% in the SWHS. The ever-smoking rate for men was 77.1% in the SCCS and 69.6% in the SMHS. Nut intake was inversely associated with risk of total mortality in all 3 cohorts (all P<.001 for trend), with adjusted HRs associated with the highest vs lowest quintiles of intake being 0.79 (95% CI, 0.73-0.86) and 0.83 (95% CI, 0.77-0.88), respectively, for the US and Shanghai cohorts. This inverse association was predominantly driven by cardiovascular disease mortality (P<.05 for trend in the US cohort; P<.001 for trend in the Shanghai cohorts). When specific types of cardiovascular disease were examined, a significant inverse association was consistently seen for ischemic heart disease in all ethnic groups (HR, 0.62; 95% CI, 0.45-0.85 in blacks; HR, 0.60; 95% CI, 0.39-0.92 in whites; and HR, 0.70; 95% CI, 0.54-0.89 in Asians for the highest vs lowest quintile of nut intake). The associations for ischemic stroke (HR, 0.77; 95% CI, 0.60-1.00 for the highest vs lowest quintile of nut intake) and hemorrhagic stroke (HR, 0.77; 95% CI, 0.60-0.99 for the highest vs lowest quintile of nut intake) were significant only in Asians. The nut-mortality association was similar for men and women and for blacks, whites, and Asians and was not modified by the presence of metabolic conditions at study enrollment.
CONCLUSIONS AND RELEVANCE - Nut consumption was associated with decreased overall and cardiovascular disease mortality across different ethnic groups and among individuals from low SES groups. Consumption of nuts, particularly peanuts given their general affordability, may be considered a cost-effective measure to improve cardiovascular health.
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20 MeSH Terms
Tissue-specific expressed antibody variable gene repertoires.
Briney BS, Willis JR, Finn JA, McKinney BA, Crowe JE
(2014) PLoS One 9: e100839
MeSH Terms: Adolescent, Adult, Antibodies, Bone Marrow, Cluster Analysis, Complementarity Determining Regions, DNA, Demography, Gene Expression Regulation, Germ Cells, High-Throughput Nucleotide Sequencing, Humans, Immunoglobulin Variable Region, Lymphoid Tissue, Middle Aged, Mucous Membrane, Mutation, Mutation Rate, Organ Specificity, RNA, Somatic Hypermutation, Immunoglobulin, V(D)J Recombination, Young Adult
Show Abstract · Added February 2, 2015
Recent developments in genetic technologies allow deep analysis of the sequence diversity of immune repertoires, but little work has been reported on the architecture of immune repertoires in mucosal tissues. Antibodies are the key to prevention of infections at the mucosal surface, but it is currently unclear whether the B cell repertoire at mucosal surfaces reflects the dominant antibodies found in the systemic compartment or whether mucosal tissues harbor unique repertoires. We examined the expressed antibody variable gene repertoires from 10 different human tissues using RNA samples derived from a large number of individuals. The results revealed that mucosal tissues such as stomach, intestine and lung possess unique antibody gene repertoires that differed substantially from those found in lymphoid tissues or peripheral blood. Mutation frequency analysis of mucosal tissue repertoires revealed that they were highly mutated, with little evidence for the presence of naïve B cells, in contrast to blood. Mucosal tissue repertoires possessed longer heavy chain complementarity determining region 3 loops than lymphoid tissue repertoires. We also noted a large increase in frequency of both insertions and deletions in the small intestine antibody repertoire. These data suggest that mucosal immune repertoires are distinct in many ways from the systemic compartment.
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23 MeSH Terms
Females with FVIII and FIX deficiency have reduced joint range of motion.
Sidonio RF, Mili FD, Li T, Miller CH, Hooper WC, DeBaun MR, Soucie M, Hemophilia Treatment Centers Network
(2014) Am J Hematol 89: 831-6
MeSH Terms: Adolescent, Adult, Aged, Body Mass Index, Case-Control Studies, Child, Child, Preschool, Cross-Sectional Studies, Demography, Factor IX, Factor VIII, Female, Hemophilia A, Hemophilia B, Humans, Joints, Middle Aged, Range of Motion, Articular, Severity of Illness Index
Show Abstract · Added October 7, 2014
Little is known about rates of joint bleeding among females with FVIII/FIX deficiency or hemophilia carriers. In a cross-sectional study, we tested the hypothesis that females with FVIII or FIX deficiency enrolled in the Universal Data Collection (UDC) project had a reduced mean overall joint range of motion (ROM) compared with historic controls from the Normal Joint Study. Demographics, clinical characteristics, and joint ROM measurements on 303 females without a bleeding disorder and 148 females with FVIII and FIX deficiency, respectively, between the ages of 2-69 years and a body mass index (BMI) ≤ 35 were compared. Multivariate linear regression was performed with the overall joint ROM (sum of the right and left ROM measurements of five joints) as the dependent variable and FVIII or FIX activity as the independent variable adjusting for age, race, BMI, and number of joint bleeds reported over the last 6 months. As FVIII and FIX activity decreased, the mean overall joint ROM became reduced and in most cases was significantly lower than that of the controls regardless of age and clinical hemophilia severity. Further investigation of reduced joint ROM as evidence of subclinical joint bleeding in females with FVIII and FIX deficiency is warranted.
© 2014 Wiley Periodicals, Inc.
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19 MeSH Terms
Demographics of animal bite victims & management practices in a tertiary care institute in Mumbai, Maharashtra, India.
Gogtay NJ, Nagpal A, Mallad A, Patel K, Stimpson SJ, Belur A, Thatte UM
(2014) Indian J Med Res 139: 459-62
MeSH Terms: Animals, Bites and Stings, Cities, Demography, Dogs, Humans, India, Rabies, Rabies Vaccines, Sex Factors, Socioeconomic Factors
Show Abstract · Added April 7, 2016
BACKGROUND & OBJECTIVES - Rabies is an important public health problem worldwide and more than 55,000 people die annually of the disease. The King Edward Memorial Hospital, Mumbai, is a tertiary referral centre where a rabies clinic runs 24 hours. In view of lack of information about the demographics of the disease in an urban environment the present study was carried out.
METHODS - Data on 1000 consecutive animal bite victims presenting to the institute in 2010 were collected over a 15 wk period. An electronic database was specially created for capturing information and was modelled on the information available from the WHO expert consultation on rabies, 2005. Economic burden from the patients' perspective was calculated using both direct and indirect costs.
RESULTS - The victims were largely males (771 subjects). The dog was the major biting animal (891, 89.1%).Bites were mainly of Category III (783, 78.3%). One twenty three subjects used indigenous treatments only for local wound care. Of the Category III bites, only 21 of 783 (2.7%) patients were prescribed human rabies immunoglobulin (HRIG) which was primarily for severe bites or bites close to or on the face. A total of 318 patients did not complete the full Essen regime of the vaccine. The median cost to the patient per bite was Rs. 220 (3.5 USD).
INTERPRETATION & CONCLUSIONS - Our findings showed that the use of HRIG was low with less than 2 per cent of the Category III patients being prescribed it. As vaccine and HRIG continue to remain expensive, the intradermal vaccine, shorter regimes like the Zagreb regime and monoclonal antibodies may offer safer and cost-effective options in the future. Further studies need to be done in different parts of the country.
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11 MeSH Terms
Randomization is not associated with socio-economic and demographic factors in a multi-center clinical trial of children with sickle cell anemia.
Roberts DO, Covert B, Rodeghier MJ, Parmar N, DeBaun MR, Thompson AA, Liem RI
(2014) Pediatr Blood Cancer 61: 1529-1535
MeSH Terms: Adolescent, Anemia, Sickle Cell, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Demography, Female, Follow-Up Studies, Humans, Male, Prognosis, Socioeconomic Factors
Show Abstract · Added October 7, 2014
BACKGROUND - Few studies have investigated factors influencing participation rates for minority children with a chronic disease in clinical trials. The Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial provides an opportunity to study the impact of demographic and socio-economic factors on randomization in a clinical trial among Black children. Our primary objective was to characterize the factors associated with successful randomization of children with sickle cell disease (SCD) and silent cerebral infarct (SCI) in the SIT Trial after initial consent.
PROCEDURE - Differences in socio-economic and demographic variables, family history and disease-related variables were determined between eligible participants who were successfully randomized and those who were not randomized following initial consent. Head of household educational level and family income were examined separately for US versus non-US sites.
RESULTS - Of 1,176 children enrolled in the SIT Trial, 1,016 (86%) completed screening. Of 208 (20%) children with qualifying SCI on pre-randomization MRI, 196 (94%) were successfully randomized. There were no differences in socio-economic, demographic, or disease-related variables between children who were or were not randomized. Participants from non-US sites were more likely to be randomized (22% vs. 12%, P = 0.011); although, randomization by country was associated with neither head of household education nor family income.
CONCLUSION - In the SIT Trial, acceptance of random allocation was not associated with socio-economic or demographic factors. Although these factors may represent barriers for some participants, they should not bias investigators caring for children with SCD in their approach to recruitment for clinical trial participation.
© 2014 Wiley Periodicals, Inc.
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13 MeSH Terms
A qualitative analysis evaluating the purposes and practices of clinical documentation.
Ho YX, Gadd CS, Kohorst KL, Rosenbloom ST
(2014) Appl Clin Inform 5: 153-68
MeSH Terms: Demography, Documentation, Health Personnel, Humans, Qualitative Research, Tennessee
Show Abstract · Added January 20, 2015
OBJECTIVES - An important challenge for biomedical informatics researchers is determining the best approach for healthcare providers to use when generating clinical notes in settings where electronic health record (EHR) systems are used. The goal of this qualitative study was to explore healthcare providers' and administrators' perceptions about the purpose of clinical documentation and their own documentation practices.
METHODS - We conducted seven focus groups with a total of 46 subjects composed of healthcare providers and administrators to collect knowledge, perceptions and beliefs about documentation from those who generate and review notes, respectively. Data were analyzed using inductive analysis to probe and classify impressions collected from focus group subjects.
RESULTS - We observed that both healthcare providers and administrators believe that documentation serves five primary domains: clinical, administrative, legal, research, education. These purposes are tied closely to the nature of the clinical note as a document shared by multiple stakeholders, which can be a source of tension for all parties who must use the note. Most providers reported using a combination of methods to complete their notes in a timely fashion without compromising patient care. While all administrators reported relying on computer-based documentation tools to review notes, they expressed a desire for a more efficient method of extracting relevant data.
CONCLUSIONS - Although clinical documentation has utility, and is valued highly by its users, the development and successful adoption of a clinical documentation tool largely depends on its ability to be smoothly integrated into the provider's busy workflow, while allowing the provider to generate a note that communicates effectively and efficiently with multiple stakeholders.
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6 MeSH Terms
Homocysteine metabolism in children with idiopathic nephrotic syndrome.
Kundal M, Saha A, Dubey NK, Kapoor K, Basak T, Bhardwaj G, Tanwar VS, Sengupta S, Batra V, Upadhayay AD, Bhatt A
(2014) Clin Transl Sci 7: 132-6
MeSH Terms: Case-Control Studies, Child, Cholesterol, Cysteine, Demography, Female, Folic Acid, Homocysteine, Humans, Male, Nephrotic Syndrome, Proteinuria, Remission Induction, Serum Albumin, Vitamin B 12
Show Abstract · Added November 3, 2017
BACKGROUND - Homocysteine metabolism is altered in children with idiopathic nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early atherosclerosis and glomerulosclerosis and may occur at time of first occurrence of idiopathic nephrotic syndrome.
METHODS - Thirty children with first episode of idiopathic nephrotic syndrome (FENS) aged 1-16 years along with 30 age- and sex-matched healthy controls were enrolled in this study. Homocysteine and cysteine were measured with HPLC; vitamin B12 and folic acid were measured with electro-chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine level in children with FENS and in controls. Secondary outcome measures were (1) plasma and urine homocysteine and cysteine levels in children with FENS at 12 weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B12 and folic acid in children with FENS, at 12 weeks and 1 year (remission).
RESULTS - Plasma homocysteine and cysteine levels were comparable to controls in children with FENS, at 12 weeks and 1-year remission. Plasma levels of vitamin B12 and folic acid were significantly decreased compared to controls in FENS due to increased urinary excretion, which normalize during remission at 12 weeks and 1 year. Urinary homocysteine and cysteine levels were significantly raised in FENS compared to controls and continued to be raised even at 12-week and 1-year remission.
CONCLUSION - Homocysteine metabolism is deranged in children with FENS. Renal effects of long-term raised urinary homocysteine levels need to be studied.
© 2014 Wiley Periodicals, Inc.
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15 MeSH Terms