Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas

Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping and genome-wide association mapping approach to search for genomic regions that may explain this observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 1272) were genotyped using Affymetrix and Illumina arrays. We inferred locus-specific genetic ancestry and compared the ancestry between cases and controls. We also performed single nucleotide polymorphism (SNP) association analyses in regions of interest. Correction for multiple-hypothesis testing was conducted using permutations (P(corrected)). We identified one region where genetic ancestry was significantly associated with breast cancer risk: 6q25 [odds ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 0.65-0.85, P= 1.1 × 10(-5), P(corrected)= 0.02]. A second region on 11p15 showed a trend towards association (OR per Indigenous American chromosome 0.77, 95% CI: 0.68-0.87, P= 4.3 × 10(-5), P(corrected)= 0.08). In both regions, breast cancer risk decreased with higher Indigenous American ancestry in concordance with observations made on global ancestry. The peak of the 6q25 signal includes the estrogen receptor 1 (ESR1) gene and 5' region, a locus previously implicated in breast cancer. Genome-wide association analysis found that a multi-SNP model explained the admixture signal in both regions. Our results confirm that the association between genetic ancestry and breast cancer risk in US Latinas is partly due to genetic differences between populations of European and Indigenous Americans origin. Fine-mapping within the 6q25 and possibly the 11p15 loci will lead to the discovery of the biologically functional variant/s behind this association.     

Using visual displays to communicate risk of cancer to women from diverse race/ethnic backgrounds

Objective

This study evaluated how well women from diverse race/ethnic groups were able to take a quantitative cancer risk statistic verbally provided to them and report it in a visual format.

Methods

Cross-sectional survey was administered in English, Spanish or Chinese, to women aged 50–80 (n = 1160), recruited from primary care practices. The survey contained breast, colorectal or cervical cancer questions regarding screening and prevention. Women were told cancer-specific lifetime risk then shown a visual display of risk and asked to indicate the specific lifetime risk. Correct indication of risk was the main outcome.

Results

Correct responses on icon arrays were 46% for breast, 55% for colon, and 44% for cervical; only 25% correctly responded to a magnifying glass graphic. Compared to Whites, African American and Latina women were significantly less likely to use the icon arrays correctly. Higher education and higher numeracy were associated with correct responses. Lower education was associated with lower numeracy.

Conclusions

Race/ethnic differences were associated with women's ability to take a quantitative cancer risk statistic verbally provided to them and report it in a visual format.

Practice implications

Systematically considering the complexity of intersecting factors such as race/ethnicity, educational level, poverty, and numeracy in most health communications is needed.     

Interpreter perspectives of in-person,telephonic, and videoconferencing medical interpretation in clinical encounters

Objective

To examine professional medical interpreters’ perspectives of in-person and remote interpreting modalities.

Methods

Survey of interpreters at three medical centers assessing satisfaction with aspects of communication using each modality, and adequacy of videoconferencing medical interpretation (VMI) and telephonic interpretation for 21 common clinical scenarios in the hospital and ambulatory care settings.

Results

52 interpreters completed the survey (73% response). All modalities were equally satisfactory for conveying information. Respondents favored in-person to telephonic interpretation for establishing rapport (95% versus 71%, p = .002) and for facilitating clinician understanding of patients’ social and cultural backgrounds (92% versus 69%, p = .002). Scenarios with substantial educational or psychosocial dimensions had no more than 70% of respondents rating telephonic interpretation as adequate (25–70%); for all of these scenarios, VMI represented an improvement (52–87%).

Conclusion

From the interpreter perspective, telephonic interpretation is satisfactory for information exchange, but less so for interpersonal aspects of communication. In scenarios where telephonic interpretation does not suffice, particularly those with substantial educational or psychosocial components, VMI offers improved communication.

Practice implications

Differences in interpreters’ perspectives of modalities based on communication needs and clinical scenario suggest mixed use of multiple modalities may be the best language access strategy.     

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.     

Kinematic characterization of functional reach to grasp in normal and in motor disabled children

The upper limb kinematics were assessed during the execution of a functional task in healthy adults, children and in children with motor disabilities (i.e. hemiplegic cerebral palsy (HCP) and movement disorders (MD)). The quantitative assessment was performed considering the time durations, the amplitude of movements at different joints and the periodicity of the acceleration patterns.

Compared to adults, healthy children showed increased motion amplitudes both at the head and at the trunk; this is suggestive of a reduced ability to stabilize the head during reaching. Furthermore, healthy children showed a reduced periodicity of the acceleration patterns which is interpreted as an indication of the on-going maturation process of the central nervous system.

Subjects with HCP and MD showed increased movement duration; however this general finding does not account for specific differences. Indeed, children with HCP showed reduced range of motion (ROM) of the shoulder on the frontal plane which is counterbalanced by the introduction of compensatory movements of the trunk. Conversely, in children with MD, the ROM is well-preserved whereas the movements of the head are increased especially at higher speed. Finally, the periodicity of the end-effect is dramatically reduced both in HCP and MD. This suggests the existence of out-of-phase corrective strokes that may indicate an increased variability of the motor control commands.

The results of this study reinforce the evidence that kinematic analysis may add valuable information to understand the developmental process in healthy children and to differentiate distinct levels of impairment in children with neurological disorders.     

Clinical radiation management for fluoroscopically guided interventional procedures

The primary goal of radiation management in interventional radiology is to minimize the unnecessary use of radiation. Clinical radiation management minimizes radiation risk to the patient without increasing other risks, such as procedural risks. A number of factors are considered when estimating the likelihood and severity of patient radiation effects. These include demographic factors, medical history factors, and procedure factors. Important aspects of the patient's medical history include coexisting diseases and genetic factors, medication use, radiation history, and pregnancy. As appropriate, these are evaluated as part of the preprocedure patient evaluation; radiation risk to the patient is considered along with other procedural risks. Dose optimization is possible through appropriate use of the basic features of interventional fluoroscopic equipment and intelligent use of dose-reducing technology. For all fluoroscopically guided interventional procedures, it is good practice to monitor radiation dose throughout the procedure and record it in the patient's medical record. Patients who have received a clinically significant radiation dose should be followed up after the procedure for possible deterministic effects. The authors recommend including radiation management as part of the departmental quality assurance program.     

Creatinine levels among Mexican Americans, Puerto Ricans, and Cuban Americans in the Hispanic Health and Nutrition Examination Survey

BACKGROUND: Although Latinos constitute the largest and fastest growing minority group in the United States, little is known about the prevalence of renal disease among different Latino subgroups. METHODS: We used data from the Hispanic Health and Nutrition Examination Survey (HHANES) to compare serum creatinine measurements among Mexican Americans, mainland Puerto Ricans, and Cuban Americans. We compared estimated creatinine clearance across Latino subgroups adjusted for demographic, clinical, and socioeconomic characteristics (including known predictors of chronic kidney disease) using survey logistic regression analysis. RESULTS: Cuban Americans had higher mean serum creatinine levels than the other groups across both gender and age categories. In multivariable analysis, Puerto Ricans [odds ratio (OR) 1.74, 95% confidence interval (CI) 1.16 to 2.60] and Cuban Americans (OR 4.59, CI 2.53 to 8.31) were more likely than the referent category of Mexican Americans to have an estimated creatinine clearance < 60 mL/min/1.73 m2. CONCLUSION: Serum creatinine levels differ substantially among Latino subgroups, suggesting national origin needs to be taken into consideration in studies of renal disease in Latinos. In addition, our findings highlight the need for more contemporary studies directly comparing both incidence rates of end-stage renal disease and measured renal function among Latino subgroups, perhaps leading to subgroup-specific prediction equations.     

Survival after dementia diagnosis in five racial/ethnic groups

Introduction

Information on anticipated survival time after dementia diagnosis among racially/ethnically diverse patients is needed to plan for care and evaluate disparities.

Cytomegalovirus (CMV) infection and risk of mortality in allogeneic hematopoietic stem cell transplantation (Allo‐HSCT): A systematic review,meta‐analysis,and meta‐regression analysis

Controversy surrounds the potential association between cytomegalovirus (CMV) infection and increased risk of mortality after allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). A systematic literature search was conducted using the PubMed, EMBASE, and Web of Science databases, assessing the association between CMV infection, as documented by the pp65 antigenemia assay or by polymerase chain reaction (PCR) using blood specimens, and overall mortality (OM) and nonrelapse mortality (NRM) in the allo‐HSCT setting. Pooled effects were estimated using the generic inverse variance random effects model. Heterogeneity was evaluated by Cochrane's Q test and I² statistics. The source of heterogeneity was investigated by meta‐regression and subgroup analyses. Twenty‐six of 1367 studies fulfilled eligibility criteria. CMV infection identified by PCR monitoring was significantly associated with an increased risk of OM and NRM (hazard ratio 1.47, 95% confidence interval [1.20‐1.81], P ≤ .001; hazard ratio 1.68, 95% confidence interval [1.14‐2.49], P = .05, respectively). In this setting, the use of preemptive antiviral therapy (PET) resulted in a twofold increased risk of OM and NRM. The estimated effect sizes were associated with allo‐HSCT modalities. Although our analyses point to an association between CMV infection and an increased risk of OM and NRM in allo‐HSCT recipients, the high heterogeneity across studies prevented drawing of robust conclusions on this matter.     

Patient Dose Reference Levels for Interventional Radiology: A National Approach

A set of patient dose reference levels (RLs) for fluoroscopically guided interventional procedures was obtained in a survey launched by the National Society of Interventional Radiology (IR), involving 10 public hospitals, as recommended by the European Medical Exposures Directive. A sample of 1391 dose values (kerma area product [KAP]) was collected randomly during clinical procedures for seven of the most frequent procedures. Third quartiles of the KAP distributions were used to set the RLs. A regular quality control of the X-ray systems and a calibration of the dose meters were performed during the survey. The fluoroscopy time and total number of digital subtraction angiography images per procedure were also analyzed. The RL values proposed were 12 Gy cm² for fistulography (hemodialysis access; sample of 180 cases), 73 Gy cm² for lower limb arteriography (685 cases), 89 Gy cm² for renal arteriography (55 cases), 80 Gy cm² for biliary drainage (205 cases), 289 Gy cm² for hepatic chemoembolization (151 cases), 94 Gy cm² for iliac stent (70 cases), and 236 Gy cm² for uterine embolization (45 cases). The provisional national RL values are lower than those obtained in a similar survey carried out in the United States from 2002 to 2004. These new values could be used to improve the practice of centers consistently working with doses higher than the RLs. This national survey also had a positive impact, as it helped increase the awareness of the members of the National Society of IR on a topic as crucial as patient dose values and programs on radiation protection. This paper was accepted as a scientific poster at the CIRSE annual meeting in Copenhagen, September 2008.