Interventions for raising breast cancer awareness in women

Background: Breast cancer continues to be the most commonly diagnosed cancer in women globally. Early detection, diagnosis and treatment of breast cancer are key to better outcomes. Since many women will discover a breast cancer symptom themselves, it is important that they are breast cancer aware i.e. have the knowledge, skills and confidence to detect breast changes and present promptly to a healthcare professional.Objectives: To assess the effectiveness of interventions for raising breast cancer awareness in women.Search methods: We searched the Cochrane Breast Cancer Group's Specialised Register (searched 25 January 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 27 January 2016), MEDLINE OvidSP (2008 to 27 January 2016), Embase (Embase.com, 2008 to 27 January 2016), the World Health Organization’s International Clinical Trials Registry Platform (ICTRP) search portal and ClinicalTrials.gov (searched 27 Feburary 2016). We also searched the reference lists of identified articles and reviews and the grey literature for conference proceedings and published abstracts. No language restriction was applied.Selection criteriaRandomised controlled trials (RCTs) focusing on interventions for raising women’s breast cancer awareness i.e. knowledge of potential breast cancer symptoms/changes and the confidence to look at and feel their breasts, using any means of delivery, i.e. one-to-one/group/mass media campaign(s).Data collection and analysis: Two authors selected studies, independently extracted data and assessed risk of bias. We reported the odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous outcomes and mean difference (MD) and standard deviation (SD) for continuous outcomes. Since it was not possible to combine data from included studies due to their heterogeneity, we present a narrative synthesis. We assessed the quality of evidence using GRADE methods.Main results: We included two RCTs involving 997 women: one RCT (867 women) randomised women to receive either a written booklet and usual care (intervention group 1), a written booklet and usual care plus a verbal interaction with a radiographer or research psychologist (intervention group 2) or usual care (control group); and the second RCT (130 women) randomised women to either an educational programme (three sessions of 60 to 90 minutes) or no intervention (control group).Knowledge of breast cancer symptoms: In the first study, knowledge of non-lump symptoms increased in intervention group 1 compared to the control group at two years postintervention, but not significantly (OR 1.1, 95% CI 0.7 to 1.6; P = 0.66; 449 women; moderate-quality evidence). Similarly, at two years postintervention, knowledge of symptoms increased in the intervention group 2 compared to the control group but not significantly (OR 1.4, 95% CI 0.9 to 2.1; P = 0.11; 434 women; moderate-quality evidence). In the second study, women’s awareness of breast cancer symptoms had increased one month post intervention in the educational group (MD 3.45, SD 5.11; 65 women; low-quality evidence) compared to the control group (MD −0.68, SD 5.93; 65 women; P < 0.001), where there was a decrease in awareness.Knowledge of age-related risk: In the first study, women’s knowledge of age-related risk of breast cancer increased, but not significantly, in intervention group 1 compared to control at two years postintervention (OR 1.8; 95% CI 0.9 to 3.5; P < 0.08; 447 women; moderate-quality evidence). Women's knowledge of risk increased significantly in intervention group 2 compared to control at two years postintervention (OR 4.8, 95% CI 2.6 to 9.0; P < 0.001; 431 women; moderate-quality evidence). In the second study, women’s perceived susceptibility (how at risk they considered themselves) to breast cancer had increased significantly one month post intervention in the educational group (MD 1.31, SD 3.57; 65 women; low-quality evidence) compared to the control group (MD −0.55, SD 3.31; 65 women; P = 0.005), where a decrease in perceived susceptibility was noted.Frequency of Breast Checking: In the first study, no significant change was noted for intervention group 1 compared to control at two years postintervention (OR 1.1, 95% CI 0.8 to 1.6; P = 0.54; 457 women; moderate-quality evidence). Monthly breast checking increased, but not significantly, in intervention group 2 compared to control at two years postintervention (OR 1.3, 95% CI 0.9 to 1.9; P = 0.14; 445 women; moderate-quality evidence). In the second study, women’s breast cancer preventive behaviours increased significantly one month post intervention in the educational group (MD 1.21, SD 2.54; 65 women; low-quality evidence) compared to the control group (MD 0.15, SD 2.94; 65 women; P < 0.045).Breast Cancer Awareness: Women’s overall breast cancer awareness did not change in intervention group 1 compared to control at two years postintervention (OR 1.8, 95% CI 0.6 to 5.30; P = 0.32; 435 women; moderate-quality evidence) while overall awareness increased in the intervention group 2 compared to control at two years postintervention (OR 8.1, 95% CI 2.7 to 25.0; P < 0.001; 420 women; moderate-quality evidence). In the second study, there was a significant increase in scores on the Health Belief Model (that included the constructs of awareness and perceived susceptibility) at one month postintervention in the educational group (mean 1.21, SD 2.54; 65 women) compared to the control group (mean 0.15, SD 2.94; 65 women; P = 0.045).Neither study reported outcomes relating to motivation to check their breasts, confidence to seek help, time from breast symptom discovery to presentation to a healthcare professional, intentions to seek help, quality of life, adverse effects of the interventions, stages of breast cancer, survival estimates or breast cancer mortality rates.Authors' conclusions: Based on the results of two RCTs, a brief intervention has the potential to increase women’s breast cancer awareness. However, findings of this review should be interpreted with caution, as GRADE assessment identified moderate-quality evidence in only one of the two studies reviewed. In addition, the included trials were heterogeneous in terms of the interventions, population studied and outcomes measured. Therefore, current evidence cannot be generalised to the wider context. Further studies including larger samples, validated outcome measures and longitudinal approaches are warranted

Materials for phantoms for terahertz pulsed imaging

Phantoms are commonly used in medical imaging for quality assurance, calibration, research and teaching. They may include test patterns or simulations of organs, but in either case a tissue substitute medium is an important component of the phantom. The aim of this work was to identify materials suitable for use as tissue substitutes for the relatively new medical imaging modality terahertz pulsed imaging. Samples of different concentrations of the candidate materials TX151 and napthol green dye were prepared, and measurements made of the frequency-dependent absorption coefficient (0.5 to 1.5 THz) and refractive index (0.5 to 1.0 THz). These results were compared qualitatively with measurements made in a similar way on samples of excised human tissue (skin, adipose tissue and striated muscle). Both materials would be suitable for phantoms where the dominant mechanism to be simulated is absorption (similar to ∼100 cm(-1) at 1 THz) and where simulation of the strength of reflections from boundaries is not important; for example, test patterns for spatial resolution measurements. Only TX151 had a frequency-dependent refractive index close to that of tissue, and could therefore be used to simulate the layered structure of skin, the complexity of microvasculature or to investigate frequency-dependent interference effects that have been noted in terahertz images

Use of a targeted, combinatorial next-generation sequencing approach for the study of bicuspid aortic valve

BACKGROUND: Bicuspid aortic valve (BAV) is the most common type of congenital heart disease with a population prevalence of 1-2%. While BAV is known to be highly heritable, mutations in single genes (such as GATA5 and NOTCH1) have been reported in few human BAV cases. Traditional gene sequencing methods are time and labor intensive, while next-generation high throughput sequencing remains costly for large patient cohorts and requires extensive bioinformatics processing. Here we describe an approach to targeted multi-gene sequencing with combinatorial pooling of samples from BAV patients. METHODS: We studied a previously described cohort of 78 unrelated subjects with echocardiogram-identified BAV. Subjects were identified as having isolated BAV or BAV associated with coarctation of aorta (BAV-CoA). BAV cusp fusion morphology was defined as right-left cusp fusion, right non-coronary cusp fusion, or left non-coronary cusp fusion. Samples were combined into 19 pools using a uniquely overlapping combinatorial design; a given mutation could be attributed to a single individual on the basis of which pools contained the mutation. A custom gene capture of 97 candidate genes was sequenced on the Illumina HiSeq 2000. Multistep bioinformatics processing was performed for base calling, variant identification, and in-silico analysis of putative disease-causing variants. RESULTS: Targeted capture identified 42 rare, non-synonymous, exonic variants involving 35 of the 97 candidate genes. Among these variants, in-silico analysis classified 33 of these variants as putative disease-causing changes. Sanger sequencing confirmed thirty-one of these variants, found among 16 individuals. There were no significant differences in variant burden among BAV fusion phenotypes or isolated BAV versus BAV-CoA. Pathway analysis suggests a role for the WNT signaling pathway in human BAV. CONCLUSION: We successfully developed a pooling and targeted capture strategy that enabled rapid and cost effective next generation sequencing of target genes in a large patient cohort. This approach identified a large number of putative disease-causing variants in a cohort of patients with BAV, including variants in 26 genes not previously associated with human BAV. The data suggest that BAV heritability is complex and polygenic. Our pooling approach saved over $39,350 compared to an unpooled, targeted capture sequencing strategy

Steric hindrance in the upper 50 kDa domain of the motor Myo2p leads to cytokinesis defects in fission yeast

Cytokinesis in many eukaryotes requires a contractile actomyosin ring that is placed at the division site. In fission yeast, which is an attractive organism for the study of cytokinesis, actomyosin ring assembly and contraction requires the myosin II heavy chain Myo2p. Although myo2-E1, a temperature-sensitive mutant defective in the upper 50 kDa domain of Myo2p, has been studied extensively, the molecular basis of the cytokinesis defect is not understood. Here, we isolate myo2-E1-Sup2, an intragenic suppressor that contains the original mutation in myo2-E1 (G345R) and a second mutation in the upper 50 kDa domain (Y297C). Unlike myo2-E1-Sup1, a previously characterized myo2-E1 suppressor, myo2-E1-Sup2 reverses actomyosin ring contraction defects in vitro and in vivo. Structural analysis of available myosin motor domain conformations suggests that a steric clash in myo2-E1, which is caused by the replacement of a glycine with a bulky arginine, is relieved in myo2-E1-Sup2 by mutation of a tyrosine to a smaller cysteine. Our work provides insight into the function of the upper 50 kDa domain of Myo2p, informs a molecular basis for the cytokinesis defect in myo2-E1, and may be relevant to the understanding of certain cardiomyopathies

Association of Physical Activity and Sedentary Behavior with Biological Markers Among U.S. Pregnant Women

BACKGROUND: To examine the association between objectively measured light-intensity and moderate-to-vigorous-intensity physical activity (MVPA), sedentary behaviors, and biological markers in a national sample of U.S. pregnant women, as few studies have examined these relationships among this population. METHODS: The sample of noninstitutionalized U.S. civilians was selected by a complex, multistage probability design. Data from the 2003–2006 National Health and Examination Survey were used. Two hundred six pregnant women were included in the data analysis. Physical activity and sedentary data were objectively measured via accelerometry (ActiGraph 7164). Biomarker data was obtained in the mobile examination center from urine, blood samples, blood pressure, and anthropometric measurements. Urine and blood samples were obtained to determine pregnancy status, C-reactive protein (CRP), high-density lipoprotein (HDL) cholesterol, total cholesterol, and cotinine as well as fasting glucose, fasting triglycerides, and fasting low-density lipoprotein (LDL) cholesterol data. Multivariable regression was employed to examine the association between physical activity, sedentary behavior, and biomarker levels. RESULTS: There was a positive association between sedentary behavior and CRP levels (beta coefficient [b] = 0.001, p = 0.02) and LDL cholesterol (b = 0.12, p = 0.02). There was an inverse association between light-intensity physical activity and CRP (b = -0.003; p = 0.008) and diastolic blood pressure (b = -0.03; p = 0.02), with those engaging in higher levels of MVPA having higher HDL cholesterol (b = 6.7; p = 0.01). CONCLUSION: Physical activity and sedentary behavior were favorably associated with various biomarkers among pregnant women, suggesting that healthcare providers should encourage pregnant women to participate in safe forms of physical activity behaviors while also reducing their amount of time spent in sedentary behaviors

Adaptive School-based Implementation of CBT (ASIC): clustered-SMART for building an optimized adaptive implementation intervention to improve uptake of mental health interventions in schools

Abstract Background Depressive and anxiety disorders affect 20–30% of school-age youth, most of whom do not receive adequate services, contributing to poor developmental and academic outcomes. Evidence-based practices (EBPs) such as cognitive behavioral therapy (CBT) can improve outcomes, but numerous barriers limit access among affected youth. Many youth try to access mental health services in schools, but school professionals (SPs: counselors, psychologists, social workers) are rarely trained adequately in CBT methods. Further, SPs face organizational barriers to providing CBT, such as lack of administrative support. Three promising implementation strategies to address barriers to school-based CBT delivery include (1) Replicating Effective Programs (REP), which deploys customized CBT packaging, didactic training in CBT, and technical assistance; (2) coaching, which extends training via live supervision to improve SP competence in CBT delivery; and (3) facilitation, which employs an organizational expert who mentors SPs in strategic thinking to promote self-efficacy in garnering administrative support. REP is a relatively low-intensity/low-cost strategy, whereas coaching and facilitation require additional resources. However, not all schools will require all three strategies. The primary aim of this study is to compare the effectiveness of a school-level adaptive implementation intervention involving REP, coaching, and facilitation versus REP alone on the frequency of CBT delivered to students by SPs and student mental health outcomes. Secondary and exploratory aims examine cost-effectiveness, moderators, and mechanisms of implementation strategies. Methods Using a clustered, sequential multiple-assignment, randomized trial (SMART) design, ≥ 200 SPs from 100 schools across Michigan will be randomized initially to receive REP vs. REP+coaching. After 8 weeks, schools that do not meet a pre-specified implementation benchmark are re-randomized to continue with the initial strategy or to augment with facilitation. Discussion EBPs need to be implemented successfully and efficiently in settings where individuals are most likely to seek care in order to gain large-scale impact on public health. Adaptive implementation interventions hold the promise of providing cost-effective implementation support. This is the first study to test an adaptive implementation of CBT for school-age youth, at a statewide level, delivered by school staff, taking an EBP to large populations with limited mental health care access. Trial registration NCT03541317 —Registered on 29 May 2018 on ClinicalTrials.gov PRShttps://deepblue.lib.umich.edu/bitstream/2027.42/145606/1/13012_2018_Article_808.pd

Translational Model for External Volume Expansion in Irradiated Skin

Introduction: External Volume Expansion (EVE) treatment has gained popularity in breast reconstruction, enriching recipient sites for fat grafting. For patients receiving radiotherapy (XRT), results of EVE use vary, partly because the effects of EVE on irradiated tissue are not well understood. Based on our previous work with EVE and XRT, we developed a new translational model to investigate the effects of EVE in the setting of chronic radiation skin injury. Methods: Twenty-Eight SKH1-E mice received 50Gy of beta-radiation to each flank. Animals were monitored until chronic radiation fibrosis developed (8 weeks). EVE was then applied to one side for 6hrs on 5 consecutive days. The opposite side served as control. Hyperspectral Imaging (HSI) was used to assess perfusion changes before and after EVE. Mice were sacrificed at 5 days (n=14) and 15 days (n=14) after last application for histological analysis. Tissue samples were stained for vascularity (CD31) and collagen composition (Picro-Sirius red). Results: All animals developed skin fibrosis 8 weeks post-radiation, and changes in perfusion verified skin damage. EVE application induced edema on treated sides. Five days post-application, both sides were hypo-perfused as seen by HSI; with the EVE side 13% more ischemic than the untreated side (p\u3c0.001). Perfusion returned to control side levels by day 15. Blood vessels increased 20% by day 5 in EVE versus control. Collagen composition showed no difference in scar index analysis. Conclusion: EVE temporarily augments radiation-induced hypo-perfusion, likely due to transient edema. Fibrosis remained unchanged after EVE, possibly accounting for the limited expansion seen in patients. It appears that EVE induces angiogenic effect but does not affect dermal collagen composition. Future efforts should focus on reducing fibrosis post radiation to allow EVE to achieve its full potential, to benefit irradiated patients

Development of a Pediatric Ebola Predictive Score, Sierra Leone1.

We compared children who were positive for Ebola virus disease (EVD) with those who were negative to derive a pediatric EVD predictor (PEP) score. We collected data on all children <13 years of age admitted to 11 Ebola holding units in Sierra Leone during August 2014-March 2015 and performed multivariable logistic regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the strongest positive predictors for EVD. The PEP score had an area under receiver operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and 44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could correctly classify 79%-90% of children and could be used to facilitate triage into risk categories, depending on the sensitivity or specificity required