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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.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.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).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.

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.

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.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.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.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.

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.

Consumers give increasing importance to the extrinsic quality attributes of meat in response to rising concerns on safety, health, convenience, ethical factors, etc. The role that attributes such as animal feeding assurance, environmentally friendly production, respect for the animal welfare, etc. play in the consumer quality evaluation process has not been studied enough. The objectives of this article were: to evaluate the importance of several extrinsic quality attributes of red meat to consumers in five European regions; to analyse the relationships between the attitude towards these attributes, available cues and factors or motivations that are important to consumers when buying meat; and to identify groups or segments of consumers according to the importance of extrinsic quality attributes. The most important extrinsic attributes found were animal feeding and origin. Environmentally friendly production and animal welfare considerations were also important. Animal feed assurance was an indicator of safety and nutritious/ healthy meat but origin was not. For some groups of consumers, respect for the environment and animal welfare were also related to healthy/safe meat. The range of attitudes consumers hold towards extrinsic attributes could constitute an opportunity to develop consumer-led meat products and further market segmentation.

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., In this propensity-matched cohort study, Laurent Billot and colleagues evaluate health service utilization among patients enrolled in the New South Wales Health Chronic Disease Management Program., Author Summary Why Was This Study Done? There is an increasing number of people living with chronic disease and whose chronic conditions lead to increased hospitalisations and expenditures for health systems. There is evidence to support the effectiveness of a variety of interventions, including self-management support and care coordination. New South Wales Health implemented the Chronic Disease Management Program to help people with chronic disease better manage their conditions in the community and commissioned an independent evaluation to assess the effect of the program on future hospitalisations, especially so-called avoidable, or “potentially preventable”, hospitalisations. What Did the Researchers Do and Find? We compared hospitalisation patterns in 30,057 individuals enrolled in the Chronic Disease Management Program to those in 30,057 similar individuals who were not part of the program and who were matched using a propensity score. We found, over an average follow-up of 15 mo, that avoidable hospitalisations appeared more frequent in those enrolled in the program (adjusted rate ratio 1.70, 95% CI 1.62 to 1.79, p < 0.001), with most of the excess related to the conditions targeted by the program such as chronic respiratory and cardiovascular diseases. Excesses were also observed for other secondary outcomes such as unplanned hospital admissions, readmissions, length of hospital stay, and emergency department presentations, but no difference was seen in mortality or non-avoidable hospitalisations. What Do These Findings Mean? The Chronic Disease Management Program may have uncovered unaddressed needs that led to increased hospitalisations related to the conditions targeted by the program. The results were consistent across outcomes and robust in sensitivity analyses; however, due to the non-randomised nature of the evaluation, one cannot exclude the possibility of unmeasured confounding that could not be accounted for by propensity matching and multivariable analyses. Other health indicators, such as data collected by general practices, might provide additional insight for the early identification of individuals who might benefit from similar programs, and might provide more sensitive measures of program effectiveness.

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.

This paper investigates the role of location in determining the presence of on- and off-farm pluriactivity. Gravity models are developed to define degrees of access to markets from farm locations, and farm household survey data from the Grampian Region of Scotland are used to test the ability of the models to explain the observed location of pluriactivity. Proximity to markets is shown to be an important factor for both tourist and non-tourist on-farm diversification, and is reflected in the location of farms with on-farm non-agricultural activities. However, there is no evidence of a relationship between access to labour market opportunities and the presence of off-farm employment at the sub-regional scale. Personal preferences concerning work location and household responsibilities may be more important in determining the presence of off-farm work than proximity to labour market opportunities. Possible refinements to the technique and policy implications are discussed.

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.Medical students, junior doctors, general practice registrars and GPs were recruited and interviewed. The interviews were semistructured, transcribed and analysed by theme.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.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.

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.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.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.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.

Meat labelling can be an important way of informing the consumer on the quality attributes of meat. However, the type of information consumers demand is not well known and there is a lack of consumer-oriented information. Thus, meat labelling requires special attention. The objectives of this paper were: to identify the type of information that is most demanded by European consumers on beef and lamb labelling; to analyse the relationships between the importance of informational cues and other aspects concerning consumer attitudes towards meat consumption and meat quality, and socio-demographic characteristics; and to identify groups of consumers according to their labelling preferences. The information cues considered most important related to the deadline for meat consumption and the origin of meat. Other important cues were nutritional information, maturation time, name of cut and, especially for beef consumers, information on the system of production and on the traceability and the quality control of the meat. Some groups or segments of consumers were identified that had significant differences in relation to the type of information demanded, purchasing motives, quality preferences, sources of information on quality they trusted most and socio-economic features. They could be briefly profiled as: 'quality/safety orientated'; 'traditional'; 'quality unconcerned/ convenience-driven' and 'origin motivated' consumers.