Hiding in plain view: the potential for commonly used drugs to reduce breast cancer mortality

Many medications have been developed for one purpose but then are found to have other clinical activities. There is tremendous interest in whether non-cancer medications may potentially have effects on breast cancer survival. In this review article, we have presented and evaluated the evidence for several commonly used over-the-counter and prescription medications - including aspirin (and other non-steroidal anti-inflammatory drugs), beta-blockers, angiotensin-converting enzyme inhibitors, statins, digoxin, and metformin - that have been evaluated among breast cancer survivors in prospective studies. Substantial scientific evidence supports the hypothesis that some of these common and relatively safe drugs may reduce breast cancer mortality among those with the disease by an amount that rivals the mortality reduction gained by currently used therapies. In particular, the evidence is strongest for aspirin (approximately 50% reduction), statins (approximately 25% reduction), and metformin (approximately 50% reduction). As these drugs are generic and inexpensive, there is little incentive for the pharmaceutical industry to fund the randomized trials that would show their effectiveness definitively. We advocate that confirmation of these findings in randomized trials be considered a high research priority, as the potential impact on human lives saved could be immense

Switching at the contacts in Ge9Sb1Te5 phase-change nanowire devices

Phase-change random access memory is a promising approach to non-volatile memory. However, the inability to secure consistent, reliable switching on a nanometre scale may limit its practical use for high density applications. Here, we report on the switching behaviour of PCRAM cells comprised of single crystalline Ge9Sb1Te5 (GST) nanowires. We show that device switching is dominated by the contacts and does not result in a resistance change within the bulk of the wire. For the devices studied, the typical contact resistance was ~30 kΩ, whereas the resistance of the GST channel was 1.8 kΩ. The applied voltage was predominately dropped across the passivating oxide on the surface of the GST nanowires, resulting in local resistive switching at the contacts and local power dissipation, which limited the endurance of the devices produced. The optimal device must balance low resistance contacts with a more resistive channel, to facilitate phase change switching within the nanowires. These results highlight the importance of contact formation on the switching properties in phase change devices and help guide the future design of more reliable neuromorphic devices

Misdiagnosis, Mistreatment, and Harm - When Medical Care Ignores Social Forces.

The Case Studies in Social Medicine demonstrate that when physicians use only biologic or individual behavioral interventions to treat diseases that stem from or are exacerbated by social factors, we risk harming the patients we seek to serve

Non-Communicable Diseases in Sub-Saharan Africa: The Case for Cohort Studies

Michelle Holmes and colleagues argue that there is an urgent need for longitudinal cohorts based in sub-Saharan Africa to address the growing burden of noncommunicable diseases in the region

Aspirin intake and breast cancer survival – a nation-wide study using prospectively recorded data in Sweden

Background: Aspirin (ASA) use has been associated with improved breast cancer survival in several prospective studies. Methods: We conducted a nested case–control study of ASA use after a breast cancer diagnosis among women using Swedish National Registries. We assessed prospectively recorded ASA exposure during several different time windows following cancer diagnosis using conditional logistic regression with breast cancer death as the main outcome. Within each six-month period of follow-up, we categorized dispensed ASA doses into three groups: 0, less than 1, and 1 or more daily doses. Results: We included 27,426 women diagnosed with breast cancer between 2005 and 2009; 1,661 died of breast cancer when followed until Dec 31, 2010. There was no association between ASA use and breast cancer death when exposure was assessed either shortly after diagnosis, or 3–12 months before the end of follow-up. Only during the period 0–6 months before the end of follow-up was ASA use at least daily compared with non-use associated with a decreased risk of breast cancer death: HR (95% CI) = 0.69 (0.56-0.86). However, in the same time-frame, those using ASA less than daily had an increased risk of breast cancer death: HR (95% CI) = 1.43 (1.09-1.87). Conclusions: Contrary to other studies, we did not find that ASA use was associated with a lower risk of death from breast cancer, except when assessed short term with no delay to death/end of follow-up, which may reflect discontinuation of ASA during terminal illness

Physical activity and breast cancer survival

Physical activity improves quality of life after a breast cancer diagnosis, and a beneficial effect on survival would be particularly welcome. Four observational studies have now reported decreased total mortality among physically active women with breast cancer; the two largest have also reported decreased breast cancer specific mortality. The estrogen pathway and the insulin pathway are two potential mechanisms by which physical activity could affect breast cancer survival. Randomized trials are ongoing but trials of lifestyle factors are notoriously challenging to perform. Women with breast cancer have little to lose and may possibly gain from moderate exercise

Prospective Evaluation of the Impact of Stress, Anxiety, and Depression on Household Income among Young Women with Early Breast Cancer from the Young and Strong Trial

Background: Young women with breast cancer tend to report lower quality of life and higher levels of stress than older women with breast cancer, and this may have implications for other psychosocial factors including finances. We sought to determine if stress, anxiety, and depression at diagnosis were associated with changes in household income over 12-months in young women with breast cancer in the United States. Methods: This study was a prospective, longitudinal cohort study comprised of women enrolled in the Young and Strong trial. Of the 467 women aged 18–45 newly diagnosed with early-stage breast cancer enrolled in the Young and Strong trial from 2012 to 2013, 356 (76%) answered income questions. Change in household income from baseline to 12 months was assessed and women were categorized as having lost, gained, maintained the same household income \u3c$100,000, or maintained household income ≥$100,000. Patient-reported stress, anxiety, and depression were assessed close to diagnosis at trial enrollment. Adjusted multinomial logistic regression models were used to compare women who lost, gained, or maintained household income ≥$100,000 to women who maintained the same household income \u3c$100,000. Results: Although most women maintained household income ≥$100,000 (37.1$100,000 (32.3%), 15.4% lost household income and 15.2% gained household income. Stress, anxiety, and depression were not associated with gaining or losing household income compared to women maintaining household incomes \u3c$100,000. Women with household incomes \u3c$50,000 had a higher risk of losing household income compared to women with household incomes ≥$50,000. Women who maintained household incomes ≥$100,000 were less likely to report financial or insurance problems. Among women who lost household income, 56% reported financial problems and 20% reported insurance problems at 12 months. Conclusions: Baseline stress, anxiety, and depression were not associated with household income changes for young women with breast cancer. However, lower baseline household income was associated with losing household income. Some young survivors encounter financial and insurance problems in the first year after diagnosis, and further support for these women should be considered

Occult Pneumothoraces in Children With Blunt Torso Trauma

Objectives Plain chest x‐ray (CXR) is often the initial screening test to identify pneumothoraces in trauma patients. Computed tomography (CT) scans can identify pneumothoraces not seen on CXR (“occult pneumothoraces”), but the clinical importance of these radiographically occult pneumothoraces in children is not well understood. The objectives of this study were to determine the proportion of occult pneumothoraces in injured children and the rate of treatment with tube thoracostomy among these children. Methods This was a planned substudy from a large prospective multicenter observational cohort study of children younger than 18 years old evaluated in emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network (PECARN) for blunt torso trauma from May 2007 to January 2010. Children with CXRs as part of their trauma evaluations were included for analysis. The faculty radiologist interpretations of the CXRs and any subsequent imaging studies, including CT scans, were reviewed for the absence or presence of pneumothoraces. An “occult pneumothorax” was defined as a pneumothorax that was not identified on CXR, but was subsequently demonstrated on cervical, chest, or abdominal CT scan. Rates of pneumothoraces and placement of tube thoracostomies and rate differences with 95% confidence intervals (CIs) were calculated. Results Of 12,044 enrolled in the parent study, 8,020 (67%) children (median age = 11.3 years, interquartile range [IQR] = 5.3 to 15.2 years) underwent CXRs in the ED, and these children make up the study population. Among these children, 4,276 had abdominal CT scans performed within 24 hours. A total of 372 of 8,020 children (4.6%; 95% CI = 4.2% to 5.1%) had pneumothoraces identified by CXR and/or CT. The CXRs visualized pneumothoraces in 148 patients (1.8%; 95% CI = 1.6% to 2.2%), including one false‐positive pneumothorax, which was identified on CXR, but was not demonstrated on CT. Occult pneumothoraces were present in 224 of 372 (60.2%; 95% CI = 55.0% to 65.2%) children with pneumothoraces. Tube thoracostomies were performed in 85 of 148 (57.4%; 95% CI = 49.0% to 65.5%) children with pneumothoraces on CXR and in 35 of 224 (15.6%; 95% CI = 11.1% to 21.1%) children with occult pneumothoraces (rate difference = –41.8%; 95% CI = –50.8 to –32.3%). Conclusions In pediatric patients with blunt torso trauma, pneumothoraces are uncommon, and most are not identified on the ED CXR. Nearly half of pneumothoraces, and most occult pneumothoraces, are managed without tube thoracostomy. Observation, including in children requiring endotracheal intubation, should be strongly considered during the initial management of children with occult pneumothoraces. Resumen Objetivos La radiografía de tórax simple (RXT) es a menudo la prueba de despistaje inicial para identificar los neumotórax en los pacientes con traumatismo. La tomografía computarizada (TC) puede identificar neumotórax no vistos en la RXT (“neumotórax ocultos”), aunque la importancia clínica de estos neumotórax radiográficamente ocultos en los niños no está muy estudiada. Los objetivos de este estudio fueron determinar la proporción de neumotórax ocultos en los niños accidentados y el porcentaje de tratamiento con tubo de toracostomía en estos niños. Metodología Subestudio diseñado a partir de un gran estudio observacional de cohorte prospectivo multicéntrico de niños menores de 18 años atendidos en los servicios de urgencias (SU) de la Pediatric Emergency Care Applied Research Network (PECARN) que habían sido evaluados por traumatismo torácico cerrado de mayo de 2007 a enero de 2010. Se incluyeron en el análisis los niños en los que la RXT fue parte de la evaluación inicial del traumatismo. Las interpretaciones del radiólogo de las RXT y de cualquier estudio de imagen posterior, incluyendo a TC, se revisaron para la ausencia o presencia de neumotórax. Se definió “neumotórax oculto” como un neumotórax que no fue identificado en la RXT pero que fue posteriormente visualizado en la TC abdominal, torócica o cervical. Se calcularon los porcentajes de neumotórax e inserción de tubo de toracostomía y las diferencias de sus porcentajes con los intervalos de confianza (IC) al 95%. Resultados De los 12.044 incluidos en el estudio principal, se llevo a cabo una RXT en el SU en 8.020 (67%) niños (mediana de edad 11,3 años, rango intercuartílico 5,3 a 15,2), que constituyeron la población de estudio. De estos niños, 4.276 tuvieron una TC realizada en las primeras 24 horas. En 372 de los 8.020 niños (4,6%; IC 95% = 4,2% a 5,1%) se identificó un neumotórax en la RXT y/o la TC. La RXT mostró neumotórax en 148 pacientes (1,8%; IC 95% = 1,6% a 2,2%), incluyendo un falso positivo de neumotórax, que fue identificado en la RXT pero que no fue demostrado en la TC. Los neumotórax ocultos estuvieron presentes en 224 de los 372 niños con neumotórax (60,2%; IC 95% = 55,0% a 65,2%). Se insertaron tubos de toracostomía en 85 de los 148 niños con neumotórax en la RXT (57,4%; IC 95% = 49,0% a 65,5%), y en 35 de los 224 niños con neumotórax oculto (15,6%; IC 95% = 11,1% a 21,1%; diferencia de porcentajes ‐41,8%; IC 95% = ‐50,8 a ‐32,3%). Conclusiones En los pacientes pediátricos con traumatismo torácico cerrado, los neumotórax son poco frecuentes, y la mayoría no son identificados en la RXT en el SU. Casi la mitad de los neumotórax, y la mayoría de los neumotórax ocultos son manejados sin tubo de toracostomía. La observación, incluyendo en los niños que requieren intubación endotraqueal, debería ser especialmente considerada durante el manejo inicial de los niños con neumotórax ocultos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106913/1/acem12344.pd

Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network

PURPOSE: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice. METHODS: Network members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs. RESULTS: The top three driver-stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing. CONCLUSION: Priorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members' experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs

Intake of specific fruits and vegetables in relation to risk of estrogen receptor-negative breast cancer among postmenopausal women. Breast Cancer Res

Abstract In previous studies of postmenopausal women, overall intake of fruits and vegetables groups has been inversely associated with estrogen receptor-negative (ER-) breast cancer. In this analysis, we prospectively examined the associations of specific fruits and vegetables with risk of ER-postmenopausal breast cancer among 75,929 women aged 38-63 years at baseline and followed for up to 24 years. Dietary data were collected seven times during this period. Cox proportional hazard models were used, adjusting for potential confounders, including a modified Alternate Mediterranean Diet score. We ascertained 792 incident cases of ER-postmenopausal breast cancer. The multivariate relative risk (RR) for every 2 servings/week consumption for total berries was 0.82 (95 % CI = 0.71-0.96, p = 0.01), and the RR for women who consumed at least one serving of blueberries a week was 0.69 (95 % CI = 0.50-0.95, p = 0.02) compared with non-consumers. Also, the RR for consuming at least 2 servings of peaches/ nectarines per week was 0.59 (95 % CI = 0.37-0.93, p = 0.02). Risk of ER-breast cancer was not associated with intakes of other specific fruits or vegetables. In conclusion, higher intake of berries and peaches was associated with lower risk of ER-breast cancer among postmenopausal women. These results are considered exploratory and need to be confirmed in further studies