Detailed Assessment of Low-Voltage Zones Localization by Cardiac MRI in Patients With Implantable Devices.

OBJECTIVES: The purpose of this study was to assess the performance and limitations of low-voltage zones (LVZ) localization by optimized late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) scar imaging in patients with cardiac implantable electronic devices (CIEDs). BACKGROUND: Scar evaluation by LGE-CMR can assist ventricular tachycardia (VT) ablation, but challenges with electroanatomical maps coregistration and presence of imaging artefacts from CIED limit accuracy. METHODS: A total of 10 patients underwent VT ablation and preprocedural LGE-CMR using wideband imaging. Scar was segmented from CMR pixel signal intensity maps using commercial software (ADAS-VT, Galgo Medical) with bespoke tools and compared with detailed electroanatomical maps (CARTO). Coregistration of EP and imaging-derived scar was performed using the aorta as a fiducial marker, and the impact of coregistration was determined by assessing intraobserver/interobserver variability and using computer simulations. Spatial smoothing was applied to assess correlation at different spatial resolutions and to reduce noise. RESULTS: Pixel signal intensity maps localized low-voltage zones (V <1.5 mV) with area under the receiver-operating characteristic curve: 0.82 (interquartile range [IQR]: 0.76-0.83), sensitivity 74% (IQR: 71%-77%), and specificity 78% (IQR: 73%-83%) and correlated with bipolar voltage (r = -0.57 [IQR: -0.68 to -0.42]) across patients. In simulations, small random shifts and rotations worsened LVZ localization in at least some cases. The use of the full aortic geometry ensured high reproducibility of LVZ localization (r >0.86 for area under the receiver-operating characteristic curve). Spatial smoothing improved localization of LVZ. Results for LVZ with V <0.5 mV were similar. CONCLUSIONS: In patients with CIEDs, novel wideband CMR sequences and personalized coregistration strategies can localize LVZ with good accuracy and may assist VT ablation procedures.

Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors.

BACKGROUND: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and non-obese women. METHODS: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. RESULTS: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10(-6)) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10(-5)). The most notable obesity-gene-hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10(-6)). CONCLUSIONS: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2 Future work is needed to develop powerful statistical methods able to detect these complex interactions. IMPACT: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780-90. ©2016 AACR.

The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer: A pooled analysis of 18 case-control studies.

PURPOSE: Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated. METHODS: From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model. RESULTS: Overall, women who completed ≤high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03-1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking. CONCLUSION: Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay.

Literally experts: expertise and the processing of analogical metaphors in pharmaceutical advertising.

This research examined differences between novices and experts in processing analogical metaphors appearing in prescription drug advertisements. In contrast to previous studies on knowledge transfer, no evidence of the superiority of experts in processing metaphors was found. The results from an experiment suggest that expert consumers were more likely to process a metaphor in an ad literally than novices. Our findings point to a condition in which the expertise effect with processing analogies is not the linear relationship assumed in previous studies.

FDA oversight of cell therapy clinical trials.

The U.S. Food and Drug Administration applies regulatory flexibility to balance benefits and risks to subjects in cell-therapy clinical trials.

Predictors of noncompliance in an oral contraceptive clinical trial.

BACKGROUND: This analysis was conducted to identify the participant characteristics associated with noncompliance in an oral contraceptive (OC) clinical trial. STUDY DESIGN: We studied ovarian suppression among normal-weight and obese women during the use of levonorgestrel (LNG)-containing combination OCs. Participants underwent twice weekly phlebotomy during the study cycle and received up to $360 for participation. Along with other study assays, we analyzed 903 specimens from 181 women to measure LNG to assess OC compliance. Consistently undetectable LNG levels indicated noncompliance. To evaluate predictors of OC noncompliance during this study, we compared the characteristics of compliant and noncompliant participants using multivariable logistic regression. We assigned each participant to a relative poverty level based on US census data; all other individual characteristics came directly from participant responses during the baseline interview. RESULTS: One hundred eighty-one women completed the study; 31 were noncompliant (17%). In multivariable analyses, poverty level was the strongest predictor of noncompliance. Compared with those women in the quartile with the lowest level of residential poverty, other women were far more likely to be noncompliant, especially women in the quartile with the greatest prevalence of poverty (adjusted odds ratio, 8.4; 95% confidence interval, 1.5-46.1). Additional factors associated with noncompliance were education level less than a bachelor's degree and Hispanic ethnicity. Other demographic and psychometric measures were not associated with compliance. CONCLUSIONS: We found that noncompliance was strongly associated with residential poverty level, an indirect measure of individual income. In the United States, poverty is associated with female obesity, Hispanic ethnicity and low education, which were also associated here with noncompliance. Study compensation may motivate poor individuals to participate in clinical trials for income. Noncompliance in clinical trials, particularly differential noncompliance, jeopardizes study validity.

Anthropometric, dietary, and hormonal correlates of serum adiponectin in Asian American women.

There is increasing evidence that adiponectin has a critical role in the development of breast cancer, but factors that influence adiponectin concentrations have not been well studied. We conducted a cross-sectional study among Asian-American controls who participated in a population-based case-control study of breast cancer. Participants were interviewed in-person and donated a blood specimen. Using multivariate models, we investigated the relationships between serum adiponectin concentrations and lifestyle factors (including adiposity and dietary factors) and serum sex-hormones and growth factors among postmenopausal women who were nonhormone-users at blood draw (n = 196). Adiponectin concentrations were significantly positively associated with green tea intake (P trend = 0.03); levels were 31% higher among those who drank green tea 4 or more times per wk (14.5 ± 1.10 µg/mL) compared with nongreen-tea-drinkers (11.0 ± 1.09 µg/mL); this association remained after adjustment for body mass index (BMI) and waist/hip ratio (WHR), both of which were significantly and inversely associated with adiponectin. Adiponectin concentrations were positively associated with sex-hormone-binding globulin (P trend < 0.0001) and the ratios of total testosterone (T)/total estradiol (E2) (P trend <0.004) after adjustment for BMI and WHR. Confirmation of our findings on green tea and adiponectin is needed.

Ethnic differences in the use of regular mammography: the multiethnic cohort.

Women's regular use of mammography over a 6 year interval was examined among women aged 45-75 in the Hawaii and Los Angeles Multiethnic Cohort (MEC). The analyses included 81,722 African American, Japanese, Latina, Native Hawaiian, and White females using self-reported mammography history from 1993 to 1998. Ninety-one percent of MEC women reported ever having a mammogram, however only 36% reported regular annual and 48% reported regular biennial mammography over the interval. Mammography was lowest among women who were obese, had a high school education or less, or who were aged 70 and over. Regular mammography use during follow-up was low compared to prior studies reporting on recent mammography. African American, Latina, and Native Hawaiian women had significantly lower annual and biennial mammography use compared to White women even after controlling for age, education, family history, body mass index and hormone therapy indicating that gaps exist in mammography that remain unexplained by known predictors of screening behavior.

Exploring the experiences and perspectives of families using a children's hospice and professionals providing hospice care to identify future research priorities for children's hospice care.

The main objective of this study is to generate a list of priority topics for children's hospice care research in Scotland from the perspective of its key stakeholders. The method consists of qualitative semi-structured interviews with families using hospice services (n = 5), four focus groups with hospice staff and volunteers (n = 44) and telephone interviews with professionals associated with the hospice (n = 18). Fourteen broad themes emerged following thematic content and interpretive analysis of the interview data. Some of the research themes were specific to certain stakeholder groups, whereas other themes were identified unanimously across all the stakeholder groups as being priority areas for future research. Increasing awareness of and improving access to children's hospice care, hospice and respite care needs of young people, community/home care and issues related to supporting the wider family arose, independently, in all three stakeholder groups as being priority topics for future research. In conclusion, a greater evidence base is required in the field of children's palliative care and the topics researched should be identified and led by those most closely involved in the hospices. Engaging families and care providers in the process of identifying research priorities resulted in the development of an extensive research agenda, which will contribute to quality hospice care for children and families.

A systematic assessment of common genetic variation in CYP11A and risk of breast cancer.

CYP11A catalyzes the rate-limiting step in the biosynthesis of sex-steroid hormones. In this study, we employed a systematic approach that involved gene resequencing and a haplotype-based analysis to investigate the relationship between common variation in CYP11A and breast cancer risk among African-Americans, Latinas, Japanese-Americans, Native Hawaiians, and Whites in the Multiethnic Cohort Study. Resequencing in a multiethnic panel of 95 advanced breast cancer cases revealed no common missense variant (> or =5% frequency). Common haplotype patterns were assessed by genotyping 36 densely spaced single nucleotide polymorphisms (SNPs) spanning 67 kb of the CYP11A locus in a multiethnic panel of subjects (n = 349; 1 SNP/1.86 kb on average). We identified one to two regions of strong linkage disequilibrium in these populations. Twelve tagging SNPs were selected to predict the common haplotypes (> or =5% frequency) in these regions with high probability (average R(h)(2) = 0.94) and were examined in a breast cancer case-control study in the Multiethnic Cohort Study (1,615 cases and 1,962 controls). A global test for differences in risk according to common haplotypes over the locus was statistically significant (P = 0.006), as were associations with haplotypes in each block (block 1 global test, P = 0.008; haplotype 1D, effect per haplotype copy, odds ratios, 1.23; 95% confidence interval, 1.03-1.48) and block 2 (global test, P = 0.016; haplotype 2F odds ratios, 1.52; 95% confidence interval, 1.15-2.01). These haplotypes were most common in Japanese-Americans and Native Hawaiians, followed by Whites then Latinas, and were rare in African-Americans (<5% frequency); the haplotype effects on risk across each group were homogeneous. Based on these findings, CYP11A deserves further consideration as a candidate breast cancer susceptibility gene.

Health care knowledge and consumer learning: the case of direct-to-consumer drug advertising.

This research develops a framework for understanding how consumers process health-related information and interact with their caregivers. The context is direct-to-consumer (DTC) advertising by pharmaceutical companies in North America. This theoretical research presents a research framework and focuses on the presentation of information in advertisements, consumer-learning processes, consumer utilization of health care knowledge, and bias in perceived risk. The paper proposes that consumers who lack expertise with prescription drugs learn from DTC ads differently than those with expertise. Further, it is proposed that consumers also process the information in DTC ads differently depending on the perceived effectiveness of the drug being advertised, and ultimately utilize the knowledge taken from the ads in many different ways, some of which may appear irrational to health care providers. By understanding how consumers interpret and learn from DTC ads, health care organizations and providers may be able to improve health care delivery and consumer outcomes.

Experiences of occupational violence in Australian urban general practice: a cross-sectional study of GPs.

OBJECTIVE: To establish the prevalence and characteristics of occupational violence in Australian urban general practice, and examine practitioner correlates of violence. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional questionnaire survey mailed to all members (n = 1085) of three urban divisions of general practice in New South Wales in August and September 2004. The three divisions were chosen to provide a range of socioeconomic status (SES) demographics. MAIN OUTCOME MEASURES: Occupational violence towards general practitioners during the previous 12 months. RESULTS: 528 GPs returned questionnaires (49% response rate). Of these, 63.7% had experienced violence in the previous year. The most common forms of violence were "low level" violence - verbal abuse (42.1%), property damage/theft (28.6%) and threats (23.1%). A smaller proportion of GPs had experienced "high level" violence, such as sexual harassment (9.3%) and physical abuse (2.7%). On univariate analysis, violence was significantly more likely towards female GPs (P < 0.001), less experienced GPs (P = 0.003) and GPs working in a lower SES status area (P < 0.001), and among practice populations encompassing greater social disadvantage (P = 0.006), mental health problems (P < 0.001), and drug- and alcohol-related problems (P < 0.001). Experience of violence was greater for younger GPs (P = 0.005) and those providing after-hours care (P = 0.033 for after-hours home visits). On multivariate analysis, a significant association persisted between high level violence and lower SES area (odds ratio [OR], 2.86), being female (OR, 5.87), having practice populations with more drug-related problems (OR, 5.77), and providing home visits during business hours (OR, 4.76). More experienced GPs encountered less violence (OR, 0.77) for every additional 5 years of practice. CONCLUSION: Occupational violence is a considerable problem in Australian urban general practice. Formal education programs in preventing and managing violence would be appropriate for GPs and doctors-in-training.

The Umgeni bridge, a resin bonded pontic using a preformed fibre post an aesthetic procedure of low biological and fiscal cost.

A missing anterior tooth or open embrasures destroys the aesthetics of a smile. The replacement of a missing anterior tooth is one of the most rewarding and challenging aspects of restorative dentistry. There are a number of techniques to do this, however, most involve the use of a technician, which means additional cost to the patient and multiple visits. In today's financial climate with practice expenses climbing and medical aid remuneration dwindling, one must seek methods to reduce costs and provide patients with more affordable dentistry. In addition, in crisis situations such as the traumatic loss of a tooth an immediate replacement technique albeit temporary is necessary. To replace a missing anterior tooth directly and immediately presents a rewarding challenge to the clinician. The Umgeni bridge named after the river that flows on the north side of Durban, is particularly useful in replacing congenitally missing laterals after completion of orthodontic treatment in the case of congenitally missing laterals and cleft palates.

Specialty service contracting.

Package pricing of specific services and procedures can be an effective cost-containment and marketing tool for payers and providers. Payers can secure fixed prices at discounted rates, and hospitals and physicians can retain and gain market share in an increasingly competitive health care market. Successful implementation of a package pricing strategy, however, requires a careful assessment of both market and operational factors. This chapter outlines how to identify opportunities for package pricing and how to establish rates and procedures.