Background & Aims
Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.
We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.
We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9).
We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.
EAC; Intestinal Metaplasia; Susceptibility; Cancer; ASE, allele-specific expression; BE, Barrett’s esophagus; BEACON, Barrett's and Esophageal Adenocarcinoma Consortium; CI, confidence interval; EAC, esophageal adenocarcinoma; eQTL, expression quantitative trait locus; GWAS, genome-wide association study; LD, linkage disequilibrium; OR, odds ratio; PC, principal component; SNP, single nucleotide polymorphism; TCGA, The Cancer Genome Atlas
Black men suffer disproportionately from hypertension (HTN). Antihypertensive medication non-adherence is a major contributor to poor blood pressure control, yet few studies consider how psychosocial functioning may impact Black men’s medication adherence. We examined direct and mediating pathways between depressive symptoms, psychosocial stressors, and substance use on antihypertensive medication non-adherence in 196 Black men enrolled in a clinical trial to improve HTN care and control. We found that greater depressive symptoms was associated with more medication non-adherence (β= 0.05, SE 0.01; p<.001). None of the psychosocial stressor variables were associated with antihypertensive medication non-adherence. Alcohol misuse was associated with more medication non-adherence (β=0.81, SE 0.26; p<.01), but it did not mediate the association between depressive symptoms and medication non-adherence. Clinicians should consider screening for depressive symptoms and alcohol misuse if patients are found to be non-adherent and should treat or refer patients to appropriate resources to address those issues.
Medication Adherence; Hypertension; Black men; Psychosocial factors
The family environment plays an important role in influencing children’s dietary behaviors. Traditionally, African American extended family members play a key role in child socialization. We examine the role of extended families in how children are socialized to adopt dietary norms. We conducted in-depth, semi-structured interviews with 24 individuals across eight family units to elicit information regarding the influences of culture and families on children’s dietary behaviors. Findings suggest that families teach children to value activities that combine quality time and enjoying food together; adults are inconsistent in how they teach children to adopt desired dietary behaviors. This work has implications for improving family-based interventions for African American children through promoting healthful behaviors that are also respectful of family dietary traditions, improving communication between adults and children, and leveraging family members as attitudinal and behavioral referents.
dietary socialization; families; African American
Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett’s esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA.
We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2
g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were two-sided, except in the case of variance-explained estimation where one-sided tests were used.
We estimated a statistically significant genetic variance explained for BE (h2
g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10−9) and for EA (h2
g = 25 %; SE = 5%; one-sided P = 2 × 10−7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10−6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD.
We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases.
Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contribute to the fetal size at birth. To define the genetic architecture underlying the newborn size, we performed a genome-wide association study (GWAS) in 4281 newborns in four ethnic groups from the Hyperglycemia and Adverse Pregnancy Outcome Study. We tested for association with newborn anthropometric traits (birth length, head circumference, birth weight, percent fat mass and sum of skinfolds) and newborn metabolic traits (cord glucose and C-peptide) under three models. Model 1 adjusted for field center, ancestry, neonatal gender, gestational age at delivery, parity, maternal age at oral glucose tolerance test (OGTT); Model 2 adjusted for Model 1 covariates, maternal body mass index (BMI) at OGTT, maternal height at OGTT, maternal mean arterial pressure at OGTT, maternal smoking and drinking; Model 3 adjusted for Model 2 covariates, maternal glucose and C-peptide at OGTT. Strong evidence for association was observed with measures of newborn adiposity (sum of skinfolds model 3 Z-score 7.356, P = 1.90×10−13, and to a lesser degree fat mass and birth weight) and a region on Chr3q25.31 mapping between CCNL and LEKR1. These findings were replicated in an independent cohort of 2296 newborns. This region has previously been shown to be associated with birth weight in Europeans. The current study suggests that association of this locus with birth weight is secondary to an effect on fat as opposed to lean body mass.
Maternal metabolism during pregnancy impacts the developing fetus, affecting offspring birth weight and adiposity. This has important implications for metabolic health later in life (e.g., offspring of mothers with pre-existing or gestational diabetes mellitus have an increased risk of metabolic disorders in childhood). To identify genetic loci associated with measures of maternal metabolism obtained during an oral glucose tolerance test at ∼28 weeks’ gestation, we performed a genome-wide association study of 4,437 pregnant mothers of European (n = 1,367), Thai (n = 1,178), Afro-Caribbean (n = 1,075), and Hispanic (n = 817) ancestry, along with replication of top signals in three additional European ancestry cohorts. In addition to identifying associations with genes previously implicated with measures of glucose metabolism in nonpregnant populations, we identified two novel genome-wide significant associations: 2-h plasma glucose and HKDC1, and fasting C-peptide and BACE2. These results suggest that the genetic architecture underlying glucose metabolism may differ, in part, in pregnancy.
Studies suggest that US Latinos have a higher prevalence of obesity than White Americans. However, obesity may differ by pre-immigration factors and Latinos’ cultural representations of ideal body image. This paper explores whether country of origin’s stage in the nutrition transition is related to Latino immigrants’ BMI category and self-perception of weight.
Primary data originated from a cross-sectional questionnaire of Latina/o immigrants in Baltimore in 2011. A convenience sample of self-identified Latinos, ≥18 years old, living in Baltimore was recruited from a community-based organization. Data for each country represented in the sample were obtained from the WHO Demographic and Health Surveys and the UN Food and Agriculture Organization. Each country was scored for its stage in the nutrition transition using a six-point scoring system. Descriptive statistics were conducted to characterize the sample. Bivariate analyses were conducted to examine the relationship between the outcome variables and the predictors. Multivariate logistic regressions were conducted to examine whether a country’s stage in the nutrition transition increased one’s odds of having an obese BMI score (≥30 kg/cm2) and perceiving one’s weight as overweight, while controlling for socio-demographic variables.
The sample (n = 149) consisted of immigrants from 12 Latin American countries. Participants lived in the US for x=10.24 years. About 40% of the sample had BMI ≥30 kg/m2 (obese). The longer Latina immigrants’ lived in the US, the less likely their country of origin’s nutrition transition score would increase their odds of having a BMI ≥30 kg/m2 (OR = 0.97 p < 0.04). The higher the country of origin’s nutrition transition score, the more likely BMI influenced Latino immigrants’ perception of their weight as above normal (OR = 1.06, p < 0.04). The effect of the nutrition transition score had a stronger effect on females than males.
These results suggest that country of origin’s nutrition transition score and gender affect Latino immigrants’ objective and subjective measures of weight. Future investigation should investigate the relationship between gender and the nutrition transition in Latin America and how the nutrition transition globalizes obesity and weight consciousness.
Nutrition transition; Latino immigrants; Obesity; Self-perceived body weight
To create an analytics platform for specifying and detecting clinical phenotypes and other derived variables in electronic health record (EHR) data for quality improvement investigations.
Materials and Methods
We have developed an architecture for an Analytic Information Warehouse (AIW). It supports transforming data represented in different physical schemas into a common data model, specifying derived variables in terms of the common model to enable their reuse, computing derived variables while enforcing invariants and ensuring correctness and consistency of data transformations, long-term curation of derived data, and export of derived data into standard analysis tools. It includes software that implements these features and a computing environment that enables secure high-performance access to and processing of large datasets extracted from EHRs.
We have implemented and deployed the architecture in production locally. The software is available as open source. We have used it as part of hospital operations in a project to reduce rates of hospital readmission within 30 days. The project examined the association of over 100 derived variables representing disease and co-morbidity phenotypes with readmissions in five years of data from our institution’s clinical data warehouse and the UHC Clinical Database (CDB). The CDB contains administrative data from over 200 hospitals that are in academic medical centers or affiliated with such centers.
Discussion and Conclusion
A widely available platform for managing and detecting phenotypes in EHR data could accelerate the use of such data in quality improvement and comparative effectiveness studies.
Healthcare analytics; Clinical data warehousing; Temporal abstraction; Quality improvement; Comparative effectiveness
The Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN) represents an unprecedented collaboration across diverse healthcare institutions including private, county, and state hospitals and health systems, a consortium of Federally Qualified Health Centers, and two Department of Veterans Affairs hospitals. CAPriCORN builds on the strengths of our institutions to develop a cross-cutting infrastructure for sustainable and patient-centered comparative effectiveness research in Chicago. Unique aspects include collaboration with the University HealthSystem Consortium to aggregate data across sites, a centralized communication center to integrate patient recruitment with the data infrastructure, and a centralized institutional review board to ensure a strong and efficient human subject protection program. With coordination by the Chicago Community Trust and the Illinois Medical District Commission, CAPriCORN will model how healthcare institutions can overcome barriers of data integration, marketplace competition, and care fragmentation to develop, test, and implement strategies to improve care for diverse populations and reduce health disparities.
Patient Centered; Clinical Data Network; Outcomes Research
BACKGROUND & AIMS
Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis.
We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent.
Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10−8: an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10−8). We also found evidence for 3 additional loci with P values less than 5.0 × 10−7: a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10−8), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10−8), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10−7).
In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.
Colon Cancer; Genetics; Risk Factors; SNP
Despite excellent breastfeeding initiation rates, physician mothers as a group are at risk of premature breastfeeding cessation. The main obstacles and reasons for breastfeeding cessation among physician mothers are work-related. We conducted this study to further explore physician mothers' personal infant feeding decisions and behavior as well as their clinical breastfeeding advocacy.
Subjects and Methods
We interviewed 80 physician mothers, mainly affiliated with the University of Florida College of Medicine (Gainesville, FL), using a questionnaire. Descriptive statistics were calculated with SPSS software version 16 (SPSS, Chicago, IL).
The 80 mothers had a total of 152 children and were able to successfully initiate breastfeeding for 97% of the infants. Although maternal goal for duration of breastfeeding had been 12 months or more for 57% of the infants, only 34% of the children were actually still breastfeeding at 12 months. In 43% of cases, physician mothers stated that breastfeeding cessation was due to demands of work. Furthermore, physician mothers who reported actively promoting breastfeeding among their female patients and housestaff had significantly longer personal breastfeeding duration compared with physician mothers who denied actively promoting breastfeeding.
Our findings not only emphasize the discrepancy between physician mothers' breastfeeding duration goal and their actual breastfeeding duration, but also highlight the association between their personal breastfeeding success and their own active breastfeeding advocacy. Whether this association is causal cannot be determined by the current study and can be examined further by prospective studies. Our results support developing and implementing workplace strategies and programs to promote breastfeeding duration among physician mothers returning to work.
Lateral column lengthening (LCL) is used to address the forefoot abduction associated with the adult acquired flatfoot. This opening wedge osteotomy can be filled with either allograft or autograft bone.
The investigators sought to determine union rates and any loss of correction in patients undergoing LCL with autograft versus allograft.
Over a 3-year period, 126 LCLs performed by five surgeons in 120 patients were reviewed. Autograft was used in 51 patients, allograft in 75 patients. Times to clinical and radiographic union were established for these patients. Any loss of correction of forefoot abduction as manifested by talonavicular uncoverage was recorded for those grafts that healed. Failure was defined as nonunion or loss of 50% or greater correction. The size of the implanted graft was assessed as a risk factor for failure.
There were 20 total failures: seven in patients with autograft and 13 in patients with allograft (p = 0.63). The size of the implanted graft was larger in those patients that did fail (p = 0.04).
The rate of nonunion and loss of correction for LCL was not significantly different between allograft and autograft. The overall rate of nonunion may be higher than has previously been reported.
lateral column lengthening; adult acquired flatfoot deformity; posterior tibial tendon; insufficiency/dysfunction; nonunion; loss of correction
Summary: Genome-wide association studies are widely used to investigate the genetic basis of diseases and traits, but they pose many computational challenges. We developed gdsfmt and SNPRelate (R packages for multi-core symmetric multiprocessing computer architectures) to accelerate two key computations on SNP data: principal component analysis (PCA) and relatedness analysis using identity-by-descent measures. The kernels of our algorithms are written in C/C++ and highly optimized. Benchmarks show the uniprocessor implementations of PCA and identity-by-descent are ∼8–50 times faster than the implementations provided in the popular EIGENSTRAT (v3.0) and PLINK (v1.07) programs, respectively, and can be sped up to 30–300-fold by using eight cores. SNPRelate can analyse tens of thousands of samples with millions of SNPs. For example, our package was used to perform PCA on 55 324 subjects from the ‘Gene-Environment Association Studies’ consortium studies.
Availability and implementation: gdsfmt and SNPRelate are available from R CRAN (http://cran.r-project.org), including a vignette. A tutorial can be found at https://www.genevastudy.org/Accomplishments/software.
Summary: GWASTools is an R/Bioconductor package for quality control and analysis of genome-wide association studies (GWAS). GWASTools brings the interactive capability and extensive statistical libraries of R to GWAS. Data are stored in NetCDF format to accommodate extremely large datasets that cannot fit within R’s memory limits. The documentation includes instructions for converting data from multiple formats, including variants called from sequencing. GWASTools provides a convenient interface for linking genotypes and intensity data with sample and single nucleotide polymorphism annotation.
Availability and implementation: GWASTools is implemented in R and is available from Bioconductor (http://www.bioconductor.org). An extensive vignette detailing a recommended work flow is included.
We aimed to inform the design of behavioral interventions by identifying patients’ and their family members’ perceived facilitators and barriers to hypertension self-management.
Materials and methods
We conducted focus groups of African American patients with hypertension and their family members to elicit their views about factors influencing patients’ hypertension self-management. We recruited African American patients with hypertension (n = 18) and their family members (n = 12) from an urban, community-based clinical practice in Baltimore, Maryland. We conducted four separate 90-minute focus groups among patients with controlled (one group) and uncontrolled (one group) hypertension, as well as their family members (two groups). Trained moderators used open-ended questions to assess participants’ perceptions regarding patient, family, clinic, and community-level factors influencing patients’ effective hypertension self-management.
Patient participants identified several facilitators (including family members’ support and positive relationships with doctors) and barriers (including competing health priorities, lack of knowledge about hypertension, and poor access to community resources) that influence their hypertension self-management. Family members also identified several facilitators (including their participation in patients’ doctor’s visits and discussions with patients’ doctors outside of visits) and barriers (including their own limited health knowledge and patients’ lack of motivation to sustain hypertension self-management behaviors) that affect their efforts to support patients’ hypertension self-management.
African American patients with hypertension and their family members reported numerous patient, family, clinic, and community-level facilitators and barriers to patients’ hypertension self-management. Patients’ and their family members’ views may help guide efforts to tailor behavioral interventions designed to improve hypertension self-management behaviors and hypertension control in minority populations.
hypertension; patient perspective; qualitative research; health disparities
Genome-wide transcriptional profiling was used to characterize the molecular underpinnings of neocortical organization in rhesus macaque, including cortical areal specialization and laminar cell type diversity. Microarray analysis of individual cortical layers across sensorimotor and association cortices identified robust and specific molecular signatures for individual cortical layers and areas, prominently involving genes associated with specialized neuronal function. Overall, transcriptome-based relationships were related to spatial proximity, being strongest between neighboring cortical areas and between proximal layers. Primary visual cortex (V1) displayed the most distinctive gene expression compared to other cortical regions in rhesus and human, both in the specialized layer 4 as well as other layers. Laminar patterns were more similar between macaque and human compared to mouse, as was the unique V1 profile that was not observed in mouse. These data provide a unique resource detailing neocortical transcription patterns in a non-human primate with great similarity in gene expression to human.
Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18).
African Americans and persons with low socioeconomic status (SES) are disproportionately affected by hypertension and receive less patient-centered care than less vulnerable patient populations. Moreover, continuing medical education (CME) and patient-activation interventions have infrequently been directed to improve the processes of care for these populations.
To compare the effectiveness of patient-centered interventions targeting patients and physicians with the effectiveness of minimal interventions for underserved groups.
Randomized controlled trial conducted from January 2002 through August 2005, with patient follow-up at 3 and 12 months, in 14 urban, community-based practices in Baltimore, Maryland.
Forty-one primary care physicians and 279 hypertension patients.
Physician communication skills training and patient coaching by community health workers.
Physician communication behaviors; patient ratings of physicians’ participatory decision-making (PDM), patient involvement in care (PIC), reported adherence to medications; systolic and diastolic blood pressure (BP) and BP control.
Visits of trained versus control group physicians demonstrated more positive communication change scores from baseline (−0.52 vs. −0.82, p = 0.04). At 12 months, the patient+physician intensive group compared to the minimal intervention group showed significantly greater improvements in patient report of physicians’ PDM (β = +6.20 vs. −5.24, p = 0.03) and PIC dimensions related to doctor facilitation (β = +0.22 vs. −0.17, p = 0.03) and information exchange (β = +0.32 vs. −0.22, p = 0.005). Improvements in patient adherence and BP control did not differ across groups for the overall patient sample. However, among patients with uncontrolled hypertension at baseline, non-significant reductions in systolic BP were observed among patients in all intervention groups—the patient+physician intensive (−13.2 mmHg), physician intensive/patient minimal (−10.6 mmHg), and the patient intensive/physician minimal (−16.8 mmHg), compared to the patient+physician minimal group (−2.0 mmHg).
Interventions that enhance physicians’ communication skills and activate patients to participate in their care positively affect patient-centered communication, patient perceptions of engagement in care, and may improve systolic BP among urban African-American and low SES patients with uncontrolled hypertension.
patient-centered care; patient–physician communication; hypertension
Despite well-publicized guidelines on the appropriate management of cardiovascular disease (CVD) and type 2 diabetes, the implementation of risk-reducing practices remains poor. This paper describes the results of a randomized controlled clinical trial evaluating the effectiveness of a comprehensive program of cardiovascular disease risk reduction delivered by nurse practitioner/community health worker (NP/CHW) teams versus enhanced usual care (EUC) to improve lipids, blood pressure, glycated hemoglobin (HbA1c), and patients’ perceptions of the quality of their chronic illness care in patients in urban community health centers.
Methods and Results
A total of 525 patients with documented cardiovascular disease, type 2 diabetes, hypercholesterolemia, or hypertension and levels of LDL-cholesterol, blood pressure or HbA1c that exceeded goals established by national guidelines were randomized to NP/CHW (n=261) or EUC (n=264) groups. The NP/CHW intervention included aggressive pharmacologic management and tailored educational and behavioral counseling for lifestyle modification and problem solving to address barriers to adherence and control. As compared to EUC, patients in the NP/CHW group had significantly greater 12 month improvement in total cholesterol (difference, 19.7mg/dL), LDL cholesterol (difference,15.9 mg/dL), triglycerides (difference, 16.3 mg/dL), systolic blood pressure (difference, 6.2 mm Hg), diastolic blood pressure (difference, 3.1 mm Hg), HbA1c (difference, 0.5%), and perceptions of the quality of their chronic illness care (difference, 1.2 points).
An intervention delivered by a NP/CHW team using individualized treatment regimens based on treat-to-target algorithms can be an effective approach to improve risk factor status and perceptions of chronic illnes care in high risk patients.
Randomized trial; Cardiovascular disease; Diabetes; Prevention
Lower socioeconomic status is associated with excess disease burden from diabetes. Diabetes self-management support interventions are needed that are effective in engaging lower income patients, addressing competing life priorities and barriers to self-care, and facilitating behavior change.
To pilot test feasibility, acceptability, and effect on disease control of a problem-based diabetes self-management training adapted for low literacy and accessibility.
Two-arm randomized controlled trial powered to detect a 0.50% change in A1C at follow-up with a 2-sided alpha of 0.05 in a pooled analysis.
Fifty-six urban African-American patients with type 2 diabetes and suboptimal blood sugar, blood pressure, or cholesterol control recruited from a diabetes registry within a university-affiliated managed care organization.
A group, problem-based diabetes self-management training designed for delivery in an intensive and a condensed program format. Three intensive and three condensed program groups were conducted during the trial.
Clinical (A1C, systolic blood pressure [SBP], diastolic blood pressure [DBP], LDL and HDL cholesterol) and behavioral (knowledge, problem solving, self-management behavior) data were measured at baseline, post-intervention, and 3 months post-intervention (corresponding with 6–9 months following baseline).
Adoption of both programs was high (>85% attendance rates, 95% retention). At 3 months post-intervention, the between-group difference in A1C change was −0.72% (p = 0.02), in favor of the intensive program. A1C reduction was partially mediated by problem-solving skill at follow-up (ß = −0.13, p = 0.04). Intensive program patients demonstrated within-group improvements in knowledge (p < 0.001), problem-solving (p = 0.01), and self-management behaviors (p = 0.04). Among the subsets of patients with suboptimal blood pressure or lipids at baseline, the intensive program yielded clinically significant individual improvements in SBP, DBP, and LDL cholesterol. Patient satisfaction and usability ratings were high for both programs.
A literacy-adapted, intensive, problem-solving-based diabetes self-management training was effective for key clinical and behavioral outcomes in a lower income patient sample.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-011-1689-6) contains supplementary material, which is available to authorized users.
diabetes; self-management; problem-solving; training
Of the 200,000 U.S. men annually diagnosed with prostate cancer, approximately 20–30% will have clinically aggressive disease. While factors such as Gleason score and tumor stage are used to assess prognosis, there are no biomarkers to identify men at greater risk for developing aggressive prostate cancer. We therefore undertook a search for genetic variants associated with risk of more aggressive disease.
A genome-wide scan was conducted in 202 prostate cancer cases with a more aggressive phenotype and 100 randomly sampled, age-matched PSA-screened negative controls. Analysis of 387,384 autosomal SNPs was followed by validation testing in an independent set of 527 cases with more aggressive and 595 cases with less aggressive prostate cancer, and 1,167 age-matched controls.
A variant on 15q13, rs6497287, was confirmed to be most strongly associated with more aggressive (pdiscovery=5.20×10−5, pvalidation=0.004) than less aggressive disease (p=0.14). Another SNP on 3q26, rs3774315, was found to be associated with prostate cancer risk however the association was not stronger for more aggressive disease.
This study provides suggestive evidence for a genetic predisposition to more aggressive prostate cancer and highlights the fact that larger studies are warranted to confirm this supposition and identify further risk variants.
These findings raise the possibility that assessment of genetic variation may one day be useful to discern men at higher risk for developing clinically significant prostate cancer.
prostate cancer; aggressive prostate cancer; GWAS; genetic variants
Despite well-publicized guidelines on the appropriate management of cardiovascular disease (CVD) and type 2 diabetes, implementation of risk-reducing practices remains poor. This paper describes the rationale and design of a randomized controlled clinical trial evaluating the effectiveness of a comprehensive program of CVD risk reduction delivered by nurse practitioner (NP)/community health worker (CHW) teams versus enhanced usual care in improving the proportion of patients in urban community health centers who achieve goal levels recommended by national guidelines for lipids, blood pressure, HbA1c and prescription of appropriate medications.
The COACH (Community Outreach and Cardiovascular Health) trial is a randomized controlled trial in which patients at federally-qualified community health centers were randomly assigned to one of two groups: comprehensive intensive management of CVD risk factors for one year by a NP/CHW team or an enhanced usual care control group.
A total of 3899 patients were assessed for eligibility and 525 were randomized. Groups were comparable at baseline on sociodemographic and clinical characteristics with the exception of statistically significant differences in total cholesterol and hemoglobin A1c.
This study is a novel amalgam of multilevel interdisciplinary strategies to translate highly efficacious therapies to low-income federally-funded health centers that care for patients who carry a disproportionate burden of CVD, type 2 diabetes and uncontrolled CVD risk factors. The impact of such a community clinic-based intervention is potentially enormous.
Randomized trial; Cardiovascular disease; Diabetes; Prevention; Case management; Translational research