Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆.

BACKGROUND: Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series. PATIENTS AND METHODS: KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting ≥6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety. RESULTS: Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6-29.6] and 42.9% (95% CI 34.1-52.0), respectively. A reduction in the sum of the major diameters of BM ≥30% occurred in 42.9% (95% CI 34.1-52.0), including 49.3% (95% CI 36.9-61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3-5.6) months and 18.9 (95% CI 17.1-21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM. CONCLUSION: This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01702571.

Simulation techniques in the anatomy curriculum: review of literature.

Modern medical education faces a problem of combining the latest technology, procedures and information with classic teaching methods. Simulation is a technique, which replaces or amplifies doctor-patient experiences in controlled conditions and therefore evokes or replicates substantial aspects of the real world in a fully interactive manner. The basic course of anatomy in medical education could be recognised as the best example of implementing new educational techniques such as simulation, into the traditional medical curriculum. The PubMed database was searched using specific key words. Finally 72 articles were accepted and were divided into 3 basic categories of teaching methods: Category 1 - cadaveric dissection, Category 2 - simulator based education and Category 3 - other. A state of the art anatomical curriculum offers numerous possibilities and solutions including the oldest like cadaveric dissection and newest like simulators. Different simulation techniques are used with different intensity; however cadaveric dissection is still the most popular method. The second most frequent method is simulation-based training, in which North America is the leading country. The identification of anatomical structures during virtual surgical procedures or laparoscopic robotic procedures can be integrated into the traditional anatomy course. New technologies are supportive and beneficial in anatomy teaching however each excitement of new technologies sometimes should be tempered and evaluated for its usefulness in making the learning process constructive for students and their future practice.

Home-Based Kidney Care, Patient Activation, and Risk Factors for CKD Progression in Zuni Indians: A Randomized, Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: The burden of CKD is greater in ethnic and racial minorities and persons living in rural communities, where access to care is limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A 12-month clinical trial was performed in 98 rural adult Zuni Indians with CKD to examine the efficacy of a home-based kidney care program. Participants were randomized by household to receive usual care or home-based care. After initial lifestyle coaching, the intervention group received frequent additional reinforcement by community health representatives about adherence to medicines, diet and exercise, self-monitoring, and coping strategies for living with stress. The primary outcome was change in patient activation score, which assesses a participant's knowledge, skill, and confidence in managing his/her own health and health care. RESULTS: Of 125 randomized individuals (63 intervention and 62 usual care), 98 (78%; 50 intervention and 48 usual care) completed the 12-month study. The average patient activation score after 12 months was 8.7 (95% confidence interval, 1.9 to 15.5) points higher in the intervention group than in the usual care group after adjusting for baseline score using linear models with generalized estimating equations. Participants randomized to the intervention had 4.8 (95% confidence interval, 1.4 to 16.7) times the odds of having a final activation level of at least three ("taking action") than those in the usual care group. Body mass index declined by 1.1 kg/m2 (P=0.01), hemoglobin A1c declined by 0.7% (P=0.01), high-sensitivity C-reactive protein declined by 3.3-fold (P<0.001), and the Short-Form 12 Health Survey mental score increased by five points (P=0.002) in the intervention group relative to usual care. CONCLUSIONS: A home-based intervention improves participants' activation in their own health and health care, and it may reduce risk factors for CKD in a rural disadvantaged population.

Perspectives on Biological Monitoring in Environmental Health Research: A Focus Group Study in a Native American Community.

Background: Reliance on natural resources brings Native American communities into frequent contact with environmental media, which, if contaminated, represents an exposure route for environmental pollutants. Native American communities vary in their perspectives on research and relatively little is known about the range of perspectives regarding the use of biological samples for environmental exposure assessment. Methods: Thirty-one members of Zuni Pueblo (median age = 40.0 years, range = 26⁻59 years) participated a series of four focus groups. Qualitative themes emerging from the focus group discussion transcripts were identified by content analysis. Results: Emergent themes included adequate informed consent, traditional beliefs, and personal choice. Conclusions: The discussions reinforced the central role of traditional values in the decision to participate in research involving biological samples for environmental exposure assessment. Decision-making required a balance between the perceived value of the proposed project and its purpose, with cultural perspectives surrounding the biological sample requested. We examine the potential for study bias and include recommendations to aid in the collaborative identification and control of unintended risks posed by the use of biological samples in environmental health studies in native communities.

Assessing knowledge and attitudes of diabetes in Zuni Indians using a culture-centered approach.

INTRODUCTION: The Zuni Pueblo, in collaboration with the University of New Mexico, have formed the Zuni Health Initiative (ZHI) engaged in community-based participatory research to plan and implement educational interventions to reduce health disparities. We conducted the first phase of ZHI study and identified barriers to healthcare. We concluded that the burden presented by these barriers ultimately translates into a lack of patient activation and engagement in their health care including for diabetes, effectively hindering adoption of healthy behaviors. METHODS: Community health representatives (CHRs) led 10 one-hour focus group sessions to elicit information on diabetes knowledge and self-management strategies at which a total of 84 people participated. Audiotapes were translated and transcribed by bilingual ZHI staff. We reduced the text to thematic categories, constructed a coding dictionary and inserted the text into NVivo 9 program. RESULTS: The focus groups revealed that despite extensive personal or family experiences with diabetes or complications, participants identified knowledge gaps in the disease progression and disease management. However, we gained insight into how many Zunis conceptualize the etiology of diabetes, risk factors associated with diabetes, sources of knowledge and self-management practices. CONCLUSION: We concluded that many of the Zuni diabetics experience significant impacts on their life when they were diagnosed with diabetes and suffered the plight of stigmatization. We further concluded that developing Zuni culture specific diabetes care should focus on family involvement with continued education.

Identifying barriers to healthcare to reduce health disparity in Zuni Indians using focus group conducted by community health workers.

The Zuni Pueblo is home to an economically disadvantaged population, which faces a public health challenge from the interrelated epidemics of obesity, diabetes and kidney disease. Efforts to decrease the impact of these epidemics have been complicated by historical, economic and cultural barriers, which may limit healthcare utilization. The NIH supported Zuni Health Initiative (ZHI) conducted a study to identify barriers to healthcare in the Zuni Pueblo. Community health representatives (CHRs) led 14 one-hour focus group sessions at which a total of 112 people participated posed unique questions that took into account the Zuni culture to elicit information on perceived barriers to healthcare. Audiotapes were translated and transcribed by bilingual ZHI staff. We reduced the text to thematic categories, constructed a coding dictionary and inserted the text into NVivo 9 program. We identified nine themes emerged regarding the barriers experienced in receiving healthcare and adhering to medical advice. These included distance; transportation; embarrassment; relating to healthcare professionals; navigating the medical system; awareness of available resources; waiting times; adhering to medication; and incentives in health promotion. In conclusion the implementation of culturally appropriate community-based health promotion programs and preventive screening techniques will improve access to healthcare and diminish health disparities.

Can the blood urea nitrogen/creatinine ratio distinguish upper from lower gastrointestinal bleeding?

We wanted to know if the blood urea nitrogen to creatinine (BUN/Cr) ratio could help distinguish upper from lower gastrointestinal bleeding. We analyzed retrospectively patients admitted to our hospital for gastrointestinal bleeding over the past 5 years. A total of 126 patients represented 74 upper bleeds and 52 lower bleeds. The mean BUN/Cr ratio was significantly higher in upper than lower bleeders, 34.8 and 17.8 respectively (p less than 0.001). No lower bleeder had a ratio of greater than or equal to 36, whereas 38% of upper bleeders had a ratio of greater than or equal to 36. The BUN/Cr ratio may be an easy, cheap method of distinguishing upper from lower gastrointestinal bleeding in some cases. A BUN/Cr ratio of greater than or equal to 36 suggests upper gastrointestinal bleeding, whereas a ratio of less than 36 is not helpful in locating the source of bleeding.