Allina Health Research Articles

Abstract P3-02-02: Predictive value of breast MRI in detecting mammographically occult contralateral breast cancer: Can we target women more likely to have contralateral breast cancer based on primary tumor clinicopathologic factors?

Abstract Background: Use of preoperative magnetic resonance imaging (MRI) staging in newly diagnosed breast cancer increases detection of synchronous contralateral breast cancer (CBC) over other screening modalities; however, it is associated with a high false positive rate, additional biopsies, extensive surgical procedures, and possibly increased psychological morbidity. Specific Aims: To determine predictors of synchronous, mammographically-occult but MRI-detected CBC in women newly diagnosed with breast cancer. Methods: We performed a retrospective review of patients at Allina Health, Abbott Northwestern Hospital who had preoperative breast MRI prior to surgical resection of their breast cancer from 2010–2014. We collected patient demographic and clinicopathologic data. To determine the association between MRI-detected CBC versus benign findings based on clinicopathologic data, we performed univariate analysis (p<0.05). Multivariate Logistic Regression was used to adjust for covariates and factors predictive of CBC. Area under the Receiver Operating Characteristic Curve provided a measure of model accuracy. Findings: 1894 patients had pre-operative MRI during the study period. Of those, 201 had suspicious findings on contralateral breast MRI requiring biopsy (table 1). Overall 3% (60/1894) had synchronous CBC (invasive carcinoma or DCIS) detected on MRI. The majority of CBCs (n=60) were stage 0 or IA (85%), ER/PgR+ (98%), HER2- (89%), and low/intermediate grade (80%). Women more likely to have mammographically-occult CBC were older (p<0.001), had lobular versus ductal index cancer (p=0.03), and had ER positive (p=0.027) or PgR positive (p=0.002) tumors. On multivariate logistic regression analysis (ROC area=0.75), PgR positive status (p=0.022), and older age (p=0.004) were predictive of CBC. With each year of additional age, odds of CBC increased by 5%. No CBC was identified in women < age 45 with high risk index cancers (ER- or HER2 +). CBC was 11 times more likely when PgR status was positive versus negative. CBCs were diagnosed significantly more frequently in patients with index cancers that were hormone receptor positive and HER2 negative compared to HER2 positive or triple negative invasive index cancers (Fisher's exact test; p=0.041). Risk of CBC by Index Cancer TypeIndex CancerCBC n (%)DCIS (n=51)15 (29)Invasive carcinoma (n=150)45 (30)ER+/HER2- (n=121)41 (34)HER2 positive (n=18)3 (17)Triple Negative (n=11)1 (9)Total (n=201)60 (30) Conclusions: Preoperative MRI is effective in detecting mammographically-occult early stage, hormone receptor positive CBC in older women. MRI-detected CBC is more common in patients originally presenting with hormone receptor positive and HER2 negative index cancers. Our results suggest that it may be possible to determine a subset of patients who are less likely to benefit from a preoperative breast MRI, an important implication in an era of increasing healthcare cost utilization awareness. Citation Format: Susnik B, Lillemoe TJ, Swenson KK, Tsai ML, Finkelstein MJ, Schneider L, Braatz CM, Krueger JL, Rueth N. Predictive value of breast MRI in detecting mammographically occult contralateral breast cancer: Can we target women more likely to have contralateral breast cancer based on primary tumor clinicopathologic factors? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-02-02.

Abstract P5-16-21: The association of higher tumor HER2 load with treatment response to neoadjuvant therapy in HER2 positive breast cancer patients

Abstract Background: Neoadjuvant therapy for HER2 positive invasive breast cancer is used to downstage tumor prior to surgery, objectively measure response, and evaluate novel therapies in clinical trials. Residual Cancer Burden (RCB) established by pathologic evaluation of post-treatment surgical specimens is a marker of tumor response to chemotherapy as well as predictor of recurrence-free survival in HER2 positive breast cancer. The relationship between the HER2 tumor load and the response to chemotherapy in not known. Specific Aims: To evaluate RCB after neoadjuvant chemotherapy and HER2-targeted treatment for HER2-positive breast cancer, and to determine clinicopathologic factors associated with treatment response as represented by RCB. Methods: This retrospective chart review included all HER2-positive breast cancer patients, stage I – III, receiving neoadjuvant chemotherapy and HER2-targeted therapy with post-treatment surgical resection at an Allina Health hospital from 2013-2016. Review of clinicopathologic variables included HER2/CEP17 ratio, HER2 absolute copies, ER/PgR status (using the H score calculation), patient age, baseline tumor size, and gross and microscopic pathology review of breast tissue specimens with RCB evaluation completed by breast pathologists. To compare factors related to response, chi-square with Monte-Carlo simulation was used to analyze dichotomous variables, and Mann Whitney U-tests were used for continuous variables. Findings: The study included 97 patients. Upon surgical resection, complete pathologic response (RCB-0) was found in 47% (46/97 patients), and partial pathologic response (RCB-I) in 15% (15/97 patients). As compared to non-responders (RCB-2 and RCB-3) the complete and partial responders (RCB-0 and RCB-1) were associated with greater HER2/CEP17 ratios (10.2 vs. 6.5; p=0.003), and greater HER2 absolute copies (25 vs. 15.8; p <0.001). Complete responders were associated with lower ER expression (H scores of 89.2 vs. 171.8; p=0.005) than non-responders, with RCB-1 responders associated with ER H-scores between RCB-0 and non-responders (H score=145.9). No significant differences were noted between responders and non-responders on age at diagnosis, pre-treatment tumor size, PgR expression, or the percentage of tumor infiltrating lymphocytes. Conclusions: The majority of patients with HER2 positive tumors show considerable benefit with neoadjuvant chemotherapy and HER2-targeted treatment (63% in our study) based on RCB assessment. Predictors of response as measured by RCB include high HER2/CEP17 ratios, high absolute copies of HER2 signals by FISH, and lower ER expression. Citation Format: Lillemoe TJ, Susnik B, Grimm E, Kang S-HL, Swenson KK, Krueger JL, Finkelstein MJ, Tsai ML. The association of higher tumor HER2 load with treatment response to neoadjuvant therapy in HER2 positive breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-21.

One Library’s Journey: History of Library Services at Abbott Northwestern

Abbott Northwestern Hospital, located in the heart of Minneapolis, Minnesota, is a 662-bed quarternary care facility, and serves as the flagship hospital for Allina Health, a nonprofit health syste...

Abstracts from Center to Advance Palliative Care National Seminar Palliative Care Everywhere: Bridging the Gaps November 12-14, 2015 San Antonio, TX.

Abstracts from Center to Advance Palliative Care National Seminar Palliative Care Everywhere: Bridging the Gaps November 12-14, 2015 San Antonio, TX.

The effectiveness of nurse-delivered aromatherapy in an acute care setting

ObjectiveTo examine the use and effectiveness of essential oil therapeutic interventions on pain, nausea, and anxiety, when provided by nurses to patients in acute hospital settings across a large health system. This study expands upon the limited body of literature on aromatherapy use among inpatients. DesignRetrospective, effectiveness study using data obtained from electronic health records. SettingTen Allina Health hospitals located in Minnesota and western Wisconsin. InterventionsNurse-delivered aromatherapy. Main Outcome MeasuresChange in patient-reported pain, anxiety, and nausea, rated before and after receiving aromatherapy using a numeric rating scale (0–10). ResultsThere were 10,262 hospital admissions during the study time frame in which nurse-delivered aromatherapy was part of patient care. The majority of admissions receiving aromatherapy were females (81.71%) and white (87.32%). Over 75% of all aromatherapy sessions were administered via inhalation. Lavender had the highest absolute frequency (49.5%) of use regardless of mode of administration, followed by ginger (21.2%), sweet marjoram (12.3%), mandarin (9.4%), and combination oils (7.6%). Sweet marjoram resulted in the largest single oil average pain change at −3.31 units (95% CI: −4.28, −2.33), while lavender and sweet marjoram had equivalent average anxiety changes at −2.73 units, and ginger had the largest single oil average change in nausea at −2.02units (95% CI: −2.55, −1.49). ConclusionsEssential oils generally resulted in significant clinical improvements based on their intended use, although each oil also showed ancillary benefits for other symptoms. Future research should explore use of additional essential oils, modes of administration, and different patient populations.

Abstract A57: Evaluation of the pathologic predictors of treatment response to neoadjuvant chemotherapy for invasive lobular breast cancer

Abstract Introduction: Neoadjuvant chemotherapy (NAC) is becoming the standard of care for locally advanced breast cancer as a tool to objectively measure treatment response prior to surgery, and to downstage tumors to permit breast conserving surgery. Invasive lobular carcinoma (ILC) comprises approximately 10% of all invasive breast cancers, but is less likely than invasive ductal carcinoma to respond to NAC. The purpose of this study was to explore pathological and molecular predictors of response to NAC in patients with ILC. Study Methods: Retrospective pathology review was conducted of all consecutive cases of non-metastatic ILC patients who had received NAC and subsequent surgery for ILC (n=32) within the Allina Health system. Pre-treatment tumor size, grade, stage, HER2 status, hormone receptor status, sub-type, Ki-67 index, and post-treatment Residual Cancer Burden (RCB) were determined by breast pathologists. Mann-Whitney U and Chi-square tests with exact methods were used to test for between group difference of responders (RCB 0-1) versus non-responders (RCB 2-3) to NAC on continuous and dichotomous variables. Multivariate logistic regression was conducted to determine significant predictors of response to NAC. Findings: On univariate analysis, pleomorphic subtype (p=.004), Ki-67 (p=0.013), and HER2 status (p=.054) were significant predictors of response to NAC. On multivariate analysis, HER2 and Ki-67 provided the most efficient model for predicting response to NAC. This model correctly classified 81.3% of patients, 81.8% of RCB 0/1 and 80% of RCB 2/3. Pleomorphic subtype was highly correlated to KI-67. Conclusions: Despite a limited sample size, this study shows that pathologic predictors (pleomorphic subtype, Ki-67, and HER2 status) are significant predictors of response to NAC, and may be useful in determining which ILC patients will benefit from NAC. This is an important finding because NAC for non-responders may delay the initiation of surgery and hormonal treatments for ILC. Citation Format: Michaela L. Tsai, Marsha J. Finkelstein, Tamera J. Lillemoe, Barbara Susnik, Erin Grimm, Sung-Hae Kang, Caitlin Kelly, Karen K. Swenson. Evaluation of the pathologic predictors of treatment response to neoadjuvant chemotherapy for invasive lobular breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A57.

Implementing a Community-Driven Research Partnership: The Backyard Initiative Community Health Survey Methods and Approach.

Background: In community-based participatory research (CBPR), issues such as creating a setting where community members drive decisions and creating culturally relevant processes remain largely underachieved. The Backyard Initiative (BYI) provided the setting for implementing a community-centered collaborative research process. The BYI is a partnership between Allina Health, the Cultural Wellness Center (CWC), and community residents to improve health. Objectives: To describe the unique community-centered method used in the 2013 BYI Community Health Survey (CHS) as a viable approach for collecting meaningful and valid health related data. With this approach, the community operates as the agent of change rather than the target. Methods: At the core was the BYI assessment team, which brought together conventional researchers and community members to collaboratively design, implement, analyze, interpret, and disseminate the CHS results. Focusing on the CHS, this structure and process permitted and facilitated important and difficult discussions about approach, content and outcomes of the research. Results: We held seven sessions (239 participants). Participants were 37% African American/African and 34% Native American, 65% female, and 72% spoke English at home. Achievement of our recruitment goals, participation of groups typically underrepresented in research, and positive community feedback were indications that the BYI approach to survey research was successful. Conclusions: The BYI CHS community-centered methods built trust among research partners and participants, engaged populations often underrepresented in research, and collected meaningful data. Our success indicates that it is possible to co-design and implement a lengthy survey to inform future research and community activities.

Implementing a Community-Driven Research Partnership: The Backyard Initiative Community Health Survey Methods and Approach

In community-based participatory research (CBPR), issues such as creating a setting where community members drive decisions and creating culturally relevant processes remain largely underachieved. The Backyard Initiative (BYI) provided the setting for implementing a community-centered collaborative research process. The BYI is a partnership between Allina Health, the Cultural Wellness Center (CWC), and community residents to improve health. To describe the unique community-centered method used in the 2013 BYI Community Health Survey (CHS) as a viable approach for collecting meaningful and valid health related data. With this approach, the community operates as the agent of change rather than the target. At the core was the BYI assessment team, which brought together conventional researchers and community members to collaboratively design, implement, analyze, interpret, and disseminate the CHS results. Focusing on the CHS, this structure and process permitted and facilitated important and difficult discussions about approach, content and outcomes of the research. We held seven sessions (239 participants). Participants were 37% African American/African and 34% Native American, 65% female, and 72% spoke English at home. Achievement of our recruitment goals, participation of groups typically underrepresented in research, and positive community feedback were indications that the BYI approach to survey research was successful. The BYI CHS community-centered methods built trust among research partners and participants, engaged populations often underrepresented in research, and collected meaningful data. Our success indicates that it is possible to co-design and implement a lengthy survey to inform future research and community activities.

Improved outcomes in the HF population through outreach from regional medical center to skilled nursing facility

In 2013 St. Francis Regional Medical Center (St. Francis) had the highest Heart Failure (HF) readmission rate (24.41%) in a 12 hospital system (Allina Health). The system goal for 2013 was 15.5%. HF readmission data identified that patients discharged to the most frequently used skilled nursing facility (SNF) had a readmission rate of 35%. A primary reason for discharging patients to this SNF is the physical attachment to the hospital, making it convenient not only for the health care team but for local families. Analysis showed that although the two facilities are physically connected, there was minimal planning or communication between them. Discussions with the SNF leadership highlighted three areas of opportunity: 1. SNF nursing staff receives minimal evidence based HF education to guide patient care. 2. The SNF has an annual staff turnover rate (24%). 3. SNF readmission case reviews identified that HF patients were discharged from the hospital prior to meeting discharge criteria (50%). Specifically, not off of IV diuretics and stable on oral diuretics for 24 hours prior to discharge.

Resilience Training: A Pilot Study of a Mindfulness-Based Program with Depressed Healthcare Professionals

Mindfulness-based programs have been primarily used to target anxiety or the prevention of relapse in recurrent depression; however, limited research has been conducted on the use of mindfulness programs for relief of current depressive symptoms. To investigate the potential effect of resilience training (RT) on symptom relief for current or recurrent depression, and other psychological/behavioral outcomes. Wait-list comparison pilot study. Penny George Institute for Health and Healing, Allina Health, Minneapolis, MN. A total of 40 actively working healthcare professionals age 18-65 years. RT is an eight-week mindfulness-based program that synergizes elements of mindfulness meditation with nutrition and exercise. The first 20 consecutive individuals meeting all eligibility criteria were assigned to the RT group. The next 20 consecutive eligible individuals were placed into the wait-list control group and had an eight-week waiting period before starting the RT program. Psychological/behavioral outcomes were measured before and after completion of the RT program and two months after completion. Wait-list participants also had measures taken just before starting on the wait-list. The RT group exhibited a 63-70% (P ≤ .01) reduction in depression, a 48% (P ≤ .01) reduction in stress, a 23% (P ≤ .01) reduction in trait anxiety, and a 52% (P ≤ .01) reduction in presenteeism (a per-employee savings of $1846 over the eight-week program). All outcomes were statistically significantly different from the wait-list group. Most improvements persisted up to two months after completion of the RT program. Further replication with a larger sample size, and enhanced control group is warranted.

240Effectiveness of a Pharmacist Driven Antibiotic Stewardship Program at Two Critical Access Hospitals Using a Remote Infectious Diseases Pharmacist

• New Ulm Medical Center (NUMC) and River Falls Area Hospital (RFAH), both part of Allina Health, are critical access hospitals (CAHs) with 62 and 25 licensed beds, respectively. • Antimicrobial stewardship programs (ASPs) improve patient care by reducing inappropriate antimicrobial use, antimicrobial resistance, and hospital-acquired infections. • Guidelines recommend an ASP be led by an ID physician and ID-trained pharmacist; however, these resources are often difficult to obtain. • The purpose of this study was to evaluate the effectiveness of a pharmacist-driven ASP in two CAHs using a remote ID pharmacist and ID pharmacy resident within the same healthcare system as the ID specialists overseeing the ASP.

Engaging Staff as Problem Solvers Leads to Continuous Improvement at Allina Health

In a Kaizen endeavor at Allina Health—a nonprofit health system in the Midwestern United States with more than 26,000 employees—nurses, doctors, dietitians, engineers, housekeepers, and all other staff in four units were encouraged to contribute ideas to solve the problems they encountered on the job. Managers at all levels used effective communication, constructive feedback, and supportive delegation to coach their efforts rather than dictate solutions from above. The results led to a wide range of process improvements that cut costs and enhanced safety, efficiency, patient satisfaction, quality, and morale. Over time, the initiative will be rolled out system‐wide toward the formation of an organizational culture that empowers every staff member to improve the flow and outcome of their daily responsibilities. © 2014 Wiley Periodicals, Inc.

…From the Editor

Collaboration, commitment to the customer, and the cultivation of international partnerships are among the salient strategies for meeting competitive challenges presented in this issue. At DHL Freight, explain Kim MacGillavry and Alan Wilson on page 6, customer experience management that collects and acts on input from both consumers and employees has helped the company distinguish itself in an operations-driven industry. On page 21, Igor Gurkov and Vladimir Kossov detail a wide range of human resources and operations strategies employed at Knauf CIS, a multinational manufacturer of construction materials, to improve quality, performance, and brand recognition in transitional economies. As Gregory Clancy and Mark Graban demonstrate in their analysis of Allina Health, a nonprofit health system in the Midwestern United States (page 35), a corporate culture that champions communications and coaching among staff members can lead to improvements in processes, customer satisfaction, and employee engagement while reducing costs. Empowering workers at every level of the organization and encouraging them to speak openly also were crucial components of the culture change effort to foster effective succession planning at Beak and Johnston, a family-owned food processor in Sydney, Australia. On page 43, William S. Harvey, Stuart Parry, and Paul Vorbach offer valuable insights from B&J's experience that can guide any organization striving to meet financial targets, even during periods of uncertainty. For some businesses, internationalization offers the fastest route to growth, explains Syed Zamberi Ahmad on page 51. In seeking new markets abroad, four leading Arabian telecommunications firms found that partnering, often with culturally like-minded businesses, helped reduce uncertainty and overcome obstacles to capture customers in new markets. Any organization eager to expand its market reach would do well to perfect its ability to respond quickly to market forces. On page 69, Shaghayegh Malekifar, Seyedeh Khadijeh Taghizadeh, Syed Abidur Rahman, and Saif Ur Rehman Khan propose a framework to help leaders understand the impact that their organization's culture can have on the way they utilize their technological resources. This critical information ultimately will position them to capably respond to the competitive challenges they face.

Clinicopathologic analysis of a large series of microinvasive breast cancer.

1129 Background: Microinvasive breast cancer (Tmic) is defined by the AJCC as extension of cancer cells beyond the basement membrane with no single focus larger than 1 mm. The clinical behavior of this entity is unclear. Most series suggest that prognosis is similar to non-invasive cancer although the literature is mixed. Surgical management typically reflects invasive breast cancer including lymph node sampling. Published incidence of nodal involvement is also variable with some small series reporting incidence as high as 20%. We present a clinicopathologic review of a large series from a community practice setting. Methods: Using the AJCC definition of Tmic, we retrospectively identified all cases treated within Allina Health System from 2001-2011. Inclusion criteria included no prior history of breast cancer and available follow-up data. Data collected included ER/PR and HER2 status (when available), margin status and surgical and adjuvant therapy. Results: 118 eligible cases were identified with a mean follow-up of 3.65 years and mean age of 56.8 years (34-88). 39 were triple negative and 29 were HER2+. ER/PR data was available on all cases, HER2 on 60. 72 were treated with mastectomy. All patients underwent axillary staging. Lymph node metastasis was identified in 2 cases (one triple negative, one HER2+). In one case the metastasis measured 0.25 mm, in the other 0.4 mm. Complete axillary dissection performed on both cases demonstrated no additional lymph node involvement. Isolated tumor cells were also identified in 9 cases. 2 cases developed local recurrence following lumpectomy and radiation, both in the ipsilateral breast. One recurred with microinvasive disease, the second with DCIS only. There were no cases of metastatic recurrence and no breast cancer associated deaths. Conclusions: The clinical behavior of microinvasive breast cancer in this series is similar to DCIS. The incidence of lymph node metastasis was low (1.7%) and there were no cases of distant metastasis. Our data supports management of microinvasive breast cancer as a subset of DCIS and suggests that the benefit of routine lymph node sampling is questionable.

S22-01 Meditation as Medication

Mindfulness-based programs have been primarily used to target anxiety or the prevention of relapse in recurrent depression; however, limited research has been conducted on the use of mindfulness programs for relief of current depressive symptoms.To investigate the potential effect of resilience training (RT) on symptom relief for current or recurrent depression, and other psychological/behavioral outcomes.Wait-list comparison pilot study.Penny George Institute for Health and Healing, Allina Health, Minneapolis, MN.A total of 40 actively working healthcare professionals age 18–65 years.RT is an eight-week mindfulness-based program that synergizes elements of mindfulness meditation with nutrition and exercise. The first 20 consecutive individuals meeting all eligibility criteria were assigned to the RT group. The next 20 consecutive eligible individuals were placed into the wait-list control group and had an eight-week waiting period before starting the RT program.Psychological/behavioral outcomes were measured before and after completion of the RT program and two months after completion. Wait-list participants also had measures taken just before starting on the wait-list.The RT group exhibited a 63–70% (P ≤ .01) reduction in depression, a 48% (P ≤ .01) reduction in stress, a 23% (P ≤ .01) reduction in trait anxiety, and a 52% (P ≤ .01) reduction in presenteeism (a per-employee savings of $1846 over the eight-week program). All outcomes were statistically significantly different from the wait-list group. Most improvements persisted up to two months after completion of the RT program.Further replication with a larger sample size, and enhanced control group is warranted.

Does Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism?

Letters3 August 2010Does Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism?Gregory A. Plotnikoff, MD, MTSGregory A. Plotnikoff, MD, MTSFrom Allina Health System, Minneapolis, MN 55440-0043.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-3-201008030-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In clinical trials of pharmaceutical agents, all participants start with the same serum level of the intervention: zero. In contrast, participants in clinical trials of nutritional agents, such as vitamin D, start with wildly varying levels.This distinction is crucial. Far too many clinical trials of nutritional interventions report neither baseline nor ending serum levels, which is a significant type II error in nutritional research. Nutritional interventions can be administered with too small of a dose or for an insufficient period. In addition, without measurement of serum levels, there is no clear means of assessing adherence or ...

The Heart of New Ulm: A Vision for the Future

Coronary artery disease (CAD) continues to be a leading cause of death in the USA and throughout the world. Allina Health System, with the Minneapolis Heart Institute at Abbott Northwestern, recently announced a long-term study in the city of New Ulm, MN, to reduce risk factors for myocardial infarction and, ultimately, reduce myocardial infarction incidence. To achieve this goal, the focus will be on health promotion interventions and primary and secondary prevention strategies for CAD that are innovative, community-wide, and able to impact individuals at home, at work, in their community, and in their health care settings. Factors considered in selecting this city included the identification of health as a priority by the community, readiness and willingness of the community to change, the ability to provide and deliver systematic care, and partnerships established across multiple disciplines and sectors centered on improved health. The following stakeholders will be engaged: the community, employers, public health, health care, and health plans. Unique aspects of the intervention include centralized healthcare, including an automated medical record; genetic testing; integrated behavioral interventions; social environmental change and social circumstances; health promotion, primary prevention and secondary prevention interventions; advanced diagnostics and imaging; and state-of-the-art therapy.