Age-Independent Preoperative Chemosensitivity and 5-Year Outcome Determined by Combined 70- and 80-Gene Signature in a Prospective Trial in Early-Stage Breast Cancer.

BACKGROUND: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status. METHODS: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) tumors. RESULTS: MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype. CONCLUSION: Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer.

Impact Evaluation of a System-Wide Chronic Disease Management Program on Health Service Utilisation: A Propensity-Matched Cohort Study.

BACKGROUND: The New South Wales Health (NSW Health) Chronic Disease Management Program (CDMP) delivers interventions to adults at risk of hospitalisation for five target chronic conditions that respond well to ambulatory care: diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, and coronary artery disease. The intervention consists of two main components: (1) care coordination across sectors (acute, ambulatory, and community care from both public and private sectors) and clinical specialties, facilitated by program care coordinators, and (2) health coaching including management of lifestyle risk factors and medications and self-management. These components were broadly prescribed by the head office of NSW Health, which funded the program, and were implemented by regional health services (local health districts) in ways that best suited their own history, environment, workforce, and patient need. We used a propensity-matched cohort study to evaluate health service utilisation after enrolment in the CDMP. METHODS AND FINDINGS: The evaluation cohort included 41,303 CDMP participants enrolled between 1 January 2011 and 31 December 2013 who experienced at least one hospital admission or emergency department (ED) presentation for a target condition in the 12 mo preceding enrolment. Potential controls were selected from patients not enrolled in the CDMP but experiencing at least one hospital admission or ED presentation over the same period. Each CDMP patient in the evaluation cohort was matched to one control using 1:1 propensity score matching. The primary outcome was avoidable hospitalisations. Secondary outcomes included avoidable readmissions, avoidable bed days, unplanned hospitalisations, unplanned readmissions, unplanned bed days, ED presentations, and all-cause death. The primary analysis consisted of 30,057 CDMP participants and 30,057 matched controls with a median follow-up of 15 mo. Of those, 25,638 (85.3%) and 25,597 (85.2%) were alive by the end of follow-up in the CDMP and control groups, respectively. Baseline characteristics (including history of health service utilisation) were well balanced between the matched groups. In both groups, utilisation peaked just before the time of enrolment/matching, declined sharply immediately following enrolment, and then continued to decrease more gradually; however, after enrolment, avoidable and unplanned health service utilisation remained higher for CDMP participants compared to controls. The adjusted yearly rate of avoidable hospital admissions was 0.57 (95% CI 0.52 to 0.62) in the CDMP group versus 0.33 (95% CI 0.31 to 0.37) in the control group (adjusted rate ratio 1.70, 95% CI 1.62 to 1.79, p < 0.001). Significant increases in service utilisation were also observed for unplanned hospitalisations (1.42, 95% CI 1.37 to 1.47, p < 0.001) and ED presentations (1.37, 95% CI 1.32 to 1.42, p < 0.001) as well as avoidable (2.00, 95% CI 1.80 to 2.22, p < 0.001) and unplanned (1.51, 95% CI 1.40 to 1.62, p < 0.001) readmissions and avoidable (1.70, 95% CI 1.59 to 1.82, p < 0.001) and unplanned (1.43, 95% CI 1.36 to 1.49, p < 0.001) bed days. No evidence of a difference was seen for all-cause death (adjusted risk ratio 0.96, 95% CI 0.96 to 1.01, p = 0.10) or non-avoidable hospitalisations (all hospitalisations minus avoidable hospitalisations; adjusted rate ratio 1.03, 95% CI 0.97 to 1.10, p = 0.26). Despite the robustness of these results to sensitivity analyses, in the absence of a randomised control group, one cannot exclude the possibility of residual or unmeasured confounding that was not controlled for by the matching process and multivariable analyses. CONCLUSIONS: Participation in the CDMP was associated with an increase in avoidable hospital admissions compared to matched controls but no difference in the rate of other types of hospitalisation or death. A possible explanation is that the program identified conditions that required participants to be hospitalised. Service utilisation decreased sharply following its peak for both groups. This finding reflects the natural tendency for high-risk patients to show reductions in use following intense phases of service utilisation and highlights that, despite the additional complexity, a carefully selected control group is essential when assessing the effectiveness of interventions on hospital use.

Health sciences librarians' awareness and assessment of the Medical Library Association Code of Ethics for Health Sciences Librarianship: the results of a membership survey.

OBJECTIVE: The Medical Library Association (MLA) Board of Directors and president charged an Ethical Awareness Task Force and recommended a survey to determine MLA members' awareness of and opinions about the current Code of Ethics for Health Sciences Librarianship. METHODS: THE TASK FORCE AND MLA STAFF CRAFTED A SURVEY TO DETERMINE: (1) awareness of the MLA code and its provisions, (2) use of the MLA code to resolve professional ethical issues, (3) consultation of other ethical codes or guides, (4) views regarding the relative importance of the eleven MLA code statements, (5) challenges experienced in following any MLA code provisions, and (6) ethical problems not clearly addressed by the code. RESULTS: Over 500 members responded (similar to previous MLA surveys), and while most were aware of the code, over 30% could not remember when they had last read or thought about it, and nearly half had also referred to other codes or guidelines. The large majority thought that: (1) all code statements were equally important, (2) none were particularly difficult or challenging to follow, and (3) the code covered every ethical challenge encountered in their professional work. IMPLICATIONS: Comments provided by respondents who disagreed with the majority views suggest that the MLA code could usefully include a supplementary guide with practical advice on how to reason through a number of ethically challenging situations that are typically encountered by health sciences librarians.

Assessment and diagnosis of chronic dyspnoea: a literature review.

Dyspnoea or breathlessness is a common presenting symptom among patients attending primary care services. This review aimed to determine whether there are clinical tools that can be incorporated into a clinical decision support system for primary care for efficient and accurate diagnosis of causes of chronic dyspnoea. We searched MEDLINE, EMBASE and Google Scholar for all literature published between 1946 and 2020. Studies that evaluated a clinical algorithm for assessment of chronic dyspnoea in patients of any age group presenting to physicians with chronic dyspnoea were included. We identified 326 abstracts, 55 papers were reviewed, and eight included. A total 2026 patients aged between 20-80 years were included, 60% were women. The duration of dyspnoea was three weeks to 25 years. All studies undertook a stepwise or algorithmic approach to the assessment of dyspnoea. The results indicate that following history taking and physical examination, the first stage should include simply performed tests such as pulse oximetry, spirometry, and electrocardiography. If the patient remains undiagnosed, the second stage includes investigations such as chest x-ray, thyroid function tests, full blood count and NT-proBNP. In the third stage patients are referred for more advanced tests such as echocardiogram and thoracic CT. If dyspnoea remains unexplained, the fourth stage of assessment will require secondary care referral for more advanced diagnostic testing such as exercise tests. Utilising this proposed stepwise approach is expected to ascertain a cause for dyspnoea for 35% of the patients in stage 1, 83% by stage 3 and >90% of patients by stage 4.

Combined 70- and 80-gene signatures identify tumors with genomically luminal biology responsive to neoadjuvant endocrine therapy and are prognostic of 5-year outcome in early-stage breast cancer.

BACKGROUND: As more patients with early-stage breast cancer receive neoadjuvant endocrine therapy (NET), there is a need for reliable biomarkers that can identify patients with HR+ HER2- tumors who are likely to benefit from NET. NBRST (NCT01479101) compared the prognostic value of the 70-gene risk classification and 80-gene molecular subtyping signatures with conventional pathological classification methods in response to neoadjuvant therapy. We evaluated the association of these signatures with clinical response and 5-year outcome of patients treated with NET. METHODS: 1091 patients with early-stage breast cancer scheduled to receive neoadjuvant therapy were prospectively enrolled into NBRST, and a sub-analysis of 67 patients treated with NET was performed. Patients received standard of care genomic testing using the 70-gene and 80-gene signatures and were treated with NET, per physician's discretion. The primary endpoint was pathologic partial response (pPR) and secondary endpoints were distant metastasis-free survival (DMFS) and overall survival (OS). Clinical benefit was defined as having a pPR or stable disease (SD) with NET. RESULTS: Overall, 94.4% of patients with genomically (g) Luminal A-Type (50.0% pPR and 44.4% SD) and 95.0% with Luminal B-Type tumors (55.0% pPR and 40.0% SD) exhibited clinical benefit. At 5 years, patients with gLuminal B tumors had significantly worse DMFS (75.6%, 95% CI 50.8-89.1) than patients with gLuminal A (91.1%; 95% CI 74.8-97.1; p = 0.047), with a similar trend for OS, albeit not significant (81.0%, 95% CI 56.9-92.4 and 91.1%, 95% CI 74.8-97.1, respectively; p = 0.13). CONCLUSIONS: Genomic assays offer a broader understanding of the underlying tumor biology, which adds precision to pathology as a preoperative risk classifier. Patients with 70-gene signature Low Risk, gLuminal A tumors treated with endocrine therapy alone have excellent 5-year outcomes. Most patients with genomically-defined Luminal A- and B-Type tumors respond well to NET, suggesting these patients may be safely treated with NET, while those with gLuminal B tumors will also require post-operative chemotherapy or CDK4/6 inhibitors to improve long-term outcomes. Overall, these findings demonstrate that genomic classification, defined by the combined 70- and 80-gene signatures, is associated with tumor response and prognostic of long-term outcomes.

Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature.

PURPOSE: The 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer. METHODS: Neoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC). RESULTS: 80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34% v 38%; P = .52), and significantly higher pCR than ER+/Luminal A (2%; P < .001) and ER+/Luminal B (6%; P < .001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR. CONCLUSION: Significant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.

Enhancing the choice of general practice as a career.

BACKGROUND: The shortage of general practitioners in Australia is likely to continue unless more doctors choose general practice as a career. The aim of this qualitative research was to explore the factors that influence students' and junior doctors' career choice, particularly in respect to choosing general practice. METHODS: Medical students, junior doctors, general practice registrars and GPs were recruited and interviewed. The interviews were semistructured, transcribed and analysed by theme. RESULTS: Themes from the 38 interviews included the experience of general practice during training, the impact of the postgraduate general practice placements program, and factors that make general practice attractive or unattractive as a career choice. DISCUSSION: There are a number of factors that contribute to medical students' and junior doctors' career choice. Attention needs to be paid to the quality of the general practice learning experience and general practice posts in the early postgraduate years, and the attractions of general practice should be promoted.

The Medical Library Association Benchmarking Network: development and implementation.

OBJECTIVE: This article explores the development and implementation of the Medical Library Association (MLA) Benchmarking Network from the initial idea and test survey, to the implementation of a national survey in 2002, to the establishment of a continuing program in 2004. Started as a program for hospital libraries, it has expanded to include other nonacademic health sciences libraries. METHODS: The activities and timelines of MLA's Benchmarking Network task forces and editorial board from 1998 to 2004 are described. RESULTS: The Benchmarking Network task forces successfully developed an extensive questionnaire with parameters of size and measures of library activity and published a report of the data collected by September 2002. The data were available to all MLA members in the form of aggregate tables. Utilization of Web-based technologies proved feasible for data intake and interactive display. A companion article analyzes and presents some of the data. MLA has continued to develop the Benchmarking Network with the completion of a second survey in 2004. CONCLUSIONS: The Benchmarking Network has provided many small libraries with comparative data to present to their administrators. It is a challenge for the future to convince all MLA members to participate in this valuable program.

The Medical Library Association Benchmarking Network: results.

OBJECTIVE: This article presents some limited results from the Medical Library Association (MLA) Benchmarking Network survey conducted in 2002. Other uses of the data are also presented. METHODS: After several years of development and testing, a Web-based survey opened for data input in December 2001. Three hundred eighty-five MLA members entered data on the size of their institutions and the activities of their libraries. The data from 344 hospital libraries were edited and selected for reporting in aggregate tables and on an interactive site in the Members-Only area of MLANET. The data represent a 16% to 23% return rate and have a 95% confidence level. RESULTS: Specific questions can be answered using the reports. The data can be used to review internal processes, perform outcomes benchmarking, retest a hypothesis, refute a previous survey findings, or develop library standards. The data can be used to compare to current surveys or look for trends by comparing the data to past surveys. CONCLUSIONS: The impact of this project on MLA will reach into areas of research and advocacy. The data will be useful in the everyday working of small health sciences libraries as well as provide concrete data on the current practices of health sciences libraries.

Findings from the most recent Medical Library Association salary survey.

OBJECTIVE: The objective is to provide information on basic issues in library management identified by the Medical Library Association's (MLA's) seventh triennial salary survey. METHODS: The survey was a Web-based questionnaire. A nonrandom sample of persons was obtained by posting messages to MLA's membership and to the MEDLIB-L e-mail discussion list. Employed MLA members and nonmembers employed in medical library settings filled out a Web-based form designed using common gateway interface (CGI) programming. RESULTS: Six hundred forty-five usable responses were analyzed by the Hay Group and presented in the MLA publication, Hay Group/MLA 2001 Compensation and Benefits Survey. Results from the 2001 survey in this article focus on pay and job satisfaction. Salary survey results since 1983 were analyzed to review trends in seniority, diversity, and pay equity. CONCLUSIONS: Given the age progression of respondents from 1983 to 2001, it is clear that succession planning is a core issue for medical libraries. Although efforts to create more diversity in medical libraries in member organizations have started to yield results, pay for white respondents has increased at a higher rate than for other racial categories. The authors found that the pay-for-performance system in the organizations of approximately two-thirds of the respondents is suboptimized and that most of the reasons medical librarians cite for leaving their organization can be addressed and potentially changed by management. Results from the eighth salary survey, slated to be conducted in the fall of 2004, will further track these trends and issues.