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Currently, appropriateness criteria evaluating when to perform total shoulder arthroplasty (TSA) is lacking. In the absence of society guidelines and limited quality evidence, the RAND/University California in Los Angeles (UCLA) method provides a suitable alternative to evaluate appropriateness and assist in clinical decision making. Given the rise in utilization, appropriateness criteria for TSA have the potential to be an extremely powerful tool for improving quality of care and controlling costs. Thus, the goal of this study was to test explicit criteria to assess the appropriateness of TSA decision making using the RAND/UCLA appropriateness method. A review of recent scientific literature to gather available evidence about the use, effectiveness, efficiency, and the risks involved in surgical intervention was performed by a shoulder/elbow fellowship trained physician. Based on pertinent variables including age, rotator cuff status, previous surgical management, mobility, symptomatology, and imaging classifications, 186 clinical scenarios were created. Appropriateness criteria for TSA were developed using a modified Delphi method with a panel consisting of American Shoulder and Elbow Surgeons (ASES) members. A second panel of ASES members rated the same scenarios, with reliability testing performed to compare groups. Panel members reached agreement in 40 (64%) indications. TSA was appropriate in 15 (24%) of indications. For patients with severe symptomatology, TSA was often appropriate for patients aged <75 years and inconclusive or inappropriate for patients aged >75 years. Among patients aged <65 years, TSA varied between appropriate and inconclusive, often dependent on Walch classification. For patients with moderate symptomatology, TSA was inappropriate or inconclusive for patients aged <65 or >75 years. When compared to the second panel's results, moderate agreement was obtained with a weighted kappa statistic of 0.56. Using the RAND/UCLA method, ASES members created an appropriateness decision tree for pertinent patient variables. This presents the data in a manner that streamlines the clinical decision-making process and allows for rapid and more reliable determination of appropriateness for practitioners. The decision tree is based on a combination of clinical experience from high-volume ASES-member surgeons and a comprehensive review of current evidence. This tool can be used as part of a broader set of factors, including individual patient characteristics, prior studies, and expert opinion, to inform clinical decision making, improve quality of care, and control costs. [ABSTRACT FROM AUTHOR]

Bioprosthetic valve thrombosis may have implications for valve function and durability. Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves. Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT. Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake. Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875) [Display omitted] [ABSTRACT FROM AUTHOR]

This review examines the application of positive psychology concepts in physical health care contexts. Positive psychology aims to promote well-being in the general population. Studies identifying character strengths associated with well-being in healthy populations are numerous. Such strengths have been classified and Positive Psychology Interventions (PPIs) have been created to further develop these strengths in individuals. Positive psychology research is increasingly being undertaken in health care contexts. The review identified that most of this research involves measuring character strengths and their association with health outcomes in patients with a range of different conditions, similar to the position in positive psychology research on non-clinical populations. More recently, PPIs are beginning to be applied to clinical populations with physical health problems and this research, although relatively scarce, is reviewed here for cancer, coronary heart disease, and diabetes. In common with PPIs being evaluated in the general population, high quality studies are scarce. Applying PPIs to patients with serious health conditions presents significant challenges to health psychologists. They must ensure that patients are dealt with appropriately and ethically, given that exaggerated claims for PPIs are made on the internet quite frequently. This is discussed along with the need for more high quality research.

• Expanding and maintaining road networks consume a large quantity of raw materials and emit greenhouse gases. • Material flow analysis tracks and quantifies materials within a system, mainly determining the road material stock. • The road material stock is continuously increasing, consisting mainly of granular material, asphalt, and concrete. • Maintenance dominates future material flows due to ageing, increasing traffic, and climate change impacts. • Uncertainties affect the comparability and significance of studies on material flow analysis of roads. • Existing studies provide a starting point for advancing circularity and climate change impact quantification. Road construction and maintenance uses enormous amounts of raw materials and energy, representing the second largest accumulated material stock in the built environment after buildings. Evaluating its stock composition and induced material flows is essential in understanding the environmental impacts of road infrastructure. In recent years, there has been an increase in the number of material flow analysis studies related to road infrastructure. The aim of this review was twofold. Firstly, understanding the materials investigated and the associated quantification approaches, and secondly, establishing implications for moving towards a circular economy approach to road management and reducing greenhouse gas emissions. The review covers 86 studies, concluding that a near-stock saturation of well-developed road networks does not cause a decrease in material demand, as ageing and climate change-affected road structures continuously require maintenance. More than 50 % of road materials used in well-developed road networks are used for maintenance. Utilising reclaimed materials eases natural resource exploitation, but various barriers still diminish its full potential. There is a need to reduce estimation uncertainties through additional or consistent data (remote sensing is increasingly used) or higher data accuracy to establish material flow analysis as a policy support tool for circular economy and greenhouse gas emission reduction. [Display omitted] [ABSTRACT FROM AUTHOR]

After anterior cruciate ligament (ACL) reconstruction surgery, achieving full range of motion and strength of the postoperative knee is critical for optimal surgical outcomes. Abnormal tissue growth and scar formation in the postoperative knee can create a block to terminal extension of the knee. Cyclops lesions are areas of granulation tissue with neovascularization and fibrous tissue formation peripherally, most commonly at the anterolateral aspect of the tibial graft site after ACL reconstruction. When these lesions block terminal extension and cause mechanical symptoms, cyclops syndrome is diagnosed, and secondary knee arthroscopy is often performed to remove this tissue to allow for full range of motion. This Technical Note describes a minimally invasive approach with the NanoScope. The NanoScope allows for decreased postoperative pain and swelling with a likely quicker recovery back to normal postoperative therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study is to develop a pre-operative prognostic model based on known pre-operative factors. A database of ultrasound (US) lesions undergoing biopsy documented US lesion size, stiffness, and patient source prospectively. Women with invasive cancer presenting between 2010 and 2015 were the study group. Breast and axillary core results and ER, PR and HER receptor status were collected prospectively. Assessment of US skin thickening, US distal enhancement and presence of chronic kidney disease (CKD) was performed retrospectively. Patient survival and cause of death were ascertained from computer records. Predictive models for (i) all-cause mortality (ACM) and (ii) breast cancer death (BCD) were built and then validated using bootstrap k -fold cross-validation. A comparison of predictive performance was made between a full cause-specific Cox model, a sub cause-specific Cox model, and a full Fine-Gray sub-distribution hazard model. 1136 patients were included in the study. The median follow-up time was 6.2 years. 125 (11%) women died from breast cancer and 155 (14%) died from other causes. For the prediction of BCD, the cause-specific Cox sub-model performed the best. The time dependent AUC begins above 0.91 in year one to 3 reducing to 0.83 in year 6. The factors included in the Cox sub model were tumour size, skin thickening, source of detection, tumour grade, ER status, pre-operative nodal metastasis and CKD. We have shown that a model based on preoperative factors can predict BCD. Such prediction if externally validated and incorporating treatment data could be useful for treatment planning and patient counselling. • Known preoperative prognostic indicators can be combined to give a prognostic model. • Such a model performs well with an area under the curve above 0.80 for the first 5 years. • In the future, if treatment data is added, a model could be used to guide decisions regarding NACT and patient counselling. [ABSTRACT FROM AUTHOR]

Oncoplastic surgery for breast cancer has increased in popularity over the last few years, with oncological safety confirmed in several studies. There are, however, limited published data on patient-reported outcomes from this surgical approach. This study assessed patient-reported outcomes of satisfaction following therapeutic mammoplasty and contralateral symmetrisation (TMCS) as part of breast cancer treatment in relation to other patient and treatment factors. The validated BREAST-Q™ breast reduction module was sent to all surviving patients who had no documented cancer recurrence and had undergone TMCS in NHS Tayside between August 2013 and August 2017. The Q-score was used to analyse data and correlate with patient clinical information, surgical, pathology and treatment factors. Ethical approval was granted by the University of Dundee ethics committee. The patient response rate to the study was 64.5% (60 of 93 patients), with a mean age of 59 years (range 41–75 years). In all domains, patients reported high levels of satisfaction with outcomes. There were strong correlations between domains with the exception of physical symptoms. Younger patients reported poorer outcomes in domains that related to satisfaction with outcomes of surgery, psychosocial aspects, sexual function and physical symptoms. Treatment with chemotherapy and/or trastuzumab and lymph node positivity were associated with poorer outcomes in a number of domains. Our results demonstrate that patients report high levels of satisfaction after TMCS, but this is influenced by age. Patient-reported outcomes that include physical and psychosocial appear to be more strongly influenced by medical treatments than surgery. [ABSTRACT FROM AUTHOR]

Superior capsule reconstruction (SCR) creates a humeral head depressor in the setting of a massive, irreparable rotator cuff tear. Recently, a 6-mm-thick acellular dermal allograft (ACD) has been shown to be noninferior to the standard fascia lata autograft in recreating native shoulder biomechanics. This paper outlines a reproducible means by which to perform an arthroscopic SCR using a 6-mm ACD. A standard diagnostic arthroscopy first assesses the integrity of the subscapularis and infraspinatus tendons. The glenoid anchors are then placed. Accessory anterior and posterolateral portals are made as well as a lateral portal by which to shuttle the graft. Suture management is paramount. Ideally allograft preparation occurs on the back table simultaneously to maintain efficiency. Suture passage through premade holes in the graft, and when the sutures have passed through and been tensioned, the graft is shuttled into place and tied down with medial and lateral row anchors in SpeedBridge fashion. The thickness of ACD has been shown to influence the ability of the reconstructed superior capsule to perform its role as a humeral head depressor. This technique describes the use of a 6-mm-thick ACD to perform an arthroscopic SCR that minimizes both donor-site morbidity and operative time. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background People vary in how they respond to symptoms. The purpose of this study was to assess whether serious disease is more likely to be present in patients who report that they take any symptoms less seriously than other people do, and to assess the reliability of a question which can be used to identify the extent to which patients take any symptom seriously. To do this we assessed whether the likelihood of detecting colorectal cancer is higher in patients who report that they take symptoms less seriously than other people do. Methods Cross sectional study of 7736 patients who had colonoscopy to find colorectal cancer. Before colonoscopy, patients completed a questionnaire on bowel symptoms and were also asked: “Compared to other people of your age and sex, how seriously do you think you take any symptoms?” Likelihood of detecting colorectal cancer according to responses to this question was assessed by logistic regression models, unadjusted and adjusted for symptoms and other known predictors of colorectal cancer. Question reliability was assessed in a different sample using percentage agreement and the kappa statistic for the answers given by each patient on two occasions. Agreement between patient and doctor responses was also assessed (n = 108). Results Patients who reported they took symptoms less seriously were 3.28 (95%CI: 2.02, 5.33) times more likely to have colorectal cancer than patients who took symptoms more seriously than others. The effect was smaller (1.85 (95%CI: 1.11, 3.09)), but remained statistically significant in models including symptoms and other predictors of colorectal cancer. The question was reliable: on repeat questioning, 70% of responses were in absolute agreement and 92% were within 1 category, kappa 57%. Patient-doctor agreement was 66%, within 1 category 92%, kappa 48%. Conclusion Patients who take their symptoms less seriously have a considerably higher likelihood of colorectal cancer than those who identify themselves as taking any symptoms more seriously than other people. The question is easy to ask and has good reliability. Doctors also reliably identify how patients assess themselves. Assessment of how seriously patients take any symptoms can contribute to the clinical assessment of a patient.

Abstract Background The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease (PD) is still poorly understood. Methods High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined. Putamen, caudate, and intracranial volumes were manually traced in the axial plane of 3D reconstructed images. Striatal nuclei volumes were normalized to intracranial volume for statistical comparison. Disease status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale. Cognitive status was assessed using global status tests and detailed neuropsychological testing. Results Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender. Caudate volumes were reduced by 11% (p = 0.001) and putamen volumes by 8.1% (p = 0.025). PD striatal volumes were not found to be significantly correlated with cognitive or motor decline. Conclusion Small, but significant reductions in the volume of both the caudate and putamen occur in PD brains. These reductions are independent of the effects of age and gender, however the relation of these reductions to the functional loss of dopamine, which is characteristic of PD, remains unclear.

Abstract Background Seventy percent of women in Scotland have at least one baby, making pregnancy an opportunity to help most young women quit smoking before their own health is irreparably compromised. By quitting during pregnancy their infants will be protected from miscarriage and still birth as well as low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. In the UK, the NICE guidelines: ‘How to stop smoking in pregnancy and following childbirth’ (June 2010) highlighted that little evidence exists in the literature to confirm the efficacy of financial incentives to help pregnant smokers to quit. Its first research recommendation was to determine: Within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? Design and methods This study is a phase II exploratory individually randomized controlled trial comparing standard care for pregnant smokers with standard care plus the additional offer of financial voucher incentives to engage with specialist cessation services and/or to quit smoking during pregnancy. Participants (n = 600) will be pregnant smokers identified at maternity booking who, when contacted by specialist cessation services, agree to having their details passed to the NHS Smokefree Pregnancy Study Helpline to discuss the trial. The NHS Smokefree Pregnancy Study Helpline will be responsible for telephone consent and follow-up in late pregnancy. The primary outcome will be self reported smoking in late pregnancy verified by cotinine measurement. An economic evaluation will refine cost data collection and assess potential cost-effectiveness while qualitative research interviews with clients and health professionals will assess the level of acceptance of this form of incentive payment. The research questions are: What is the likely therapeutic efficacy? Are incentives potentially cost-effective? Is individual randomization an efficient trial design without introducing outcome bias? Can incentives be introduced in a way that is feasible and acceptable? Discussion This phase II trial will establish a workable design to reduce the risks associated with a future definitive phase III multicenter randomized controlled trial and establish a framework to assess the costs and benefits of financial incentives to help pregnant smokers to quit. Trial registration Current Controlled Trials ISRCTN87508788

Abstract Background Public policy and clinical treatment in tobacco addiction in the UK has focused on cessation: an abrupt attempt to stop all cigarettes. However, recent evidence suggests that allowing more gradual withdrawal from tobacco or even permanent partial substitution by nicotine replacement therapy (NRT) could lead to net benefits to public health. No jurisdiction has introduced smoking reduction programmes in normal clinical care and the best methods for their implementation is uncertain. Community pharmacists offering smoking cessation services in the UK are ideally placed to implement reduction programmes. This pilot study aims therefore to examine the feasibility of implementing smoking reduction programme in pharmacies, and also to see if behavioural support and a longer treatment affect the success rate for cessation. Design and methods This is a 2 × 2 randomised factorial trial of behavioural support versus no support and short versus standard length reduction programme. The pharmacists will recruit 16 patients per pharmacy, 160 smokers altogether. Pharmacists will randomise each participant by sealed envelopes. In a standard supported programme, the pharmacist will give support for 34 weeks, inviting participants to set a treatment goal and providing advice on how to reduce cigarette use. Participants in the short programme will be given the same advice on how to reduce but will reduce smoking over four weeks. Participants in the no support arms will be given a leaflet that describes the reduction programmes in 4-week and 34-week format. All participants are encouraged to use of NRT to support the reduction. These processes will be measured by recording the number of recruited smokers; percentage of those who reduce and sustain their consumption to at least 50% of baseline value, and the proportion of people who attain 4 weeks abstinence and 6 months abstinence. Interviews will assess smokers' and pharmacists' views on the way the programme ran. Discussion This is a pilot study to assess the feasibility of offering smoking reduction programme within pharmacies that offer naturalistic setting to show population benefit from these programmes. Findings from this trial will inform the development of evidence-based treatment for smokers who want to reduce and best approaches to engage reluctant quitters onto the programme. Trial Registration Current Controlled Trials ISRCTN 2010-019259-24

Abstract Background Alcohol problems are a major UK and international public health issue. The prevalence of alcohol problems is markedly higher among prisoners than the general population. However, studies suggest alcohol problems among prisoners are under-detected, under-recorded and under-treated. Identifying offenders with alcohol problems is fundamental to providing high quality healthcare. This paper reports use of the AUDIT screening tool to assess alcohol problems among prisoners. Methods Universal screening was undertaken over ten weeks with all entrants to one male Scottish prison using the AUDIT standardised screening tool and supplementary contextual questions. The questionnaire was administered by trained prison officers during routine admission procedures. Overall 259 anonymised completed questionnaires were analysed. Results AUDIT scores showed a high prevalence of alcohol problems with 73% of prisoner scores indicating an alcohol use disorder (8+), including 36% having scores indicating 'possible dependence' (20-40). AUDIT scores indicating 'possible dependence' were most apparent among 18-24 and 40-64 year-olds (40% and 56% respectively). However, individual questions showed important differences, with younger drinkers less likely to demonstrate habitual and addictive behaviours than the older age group. Disparity between high levels of harmful/hazardous/dependent drinking and low levels of 'treatment' emerged (only 27% of prisoners with scores indicating 'possible dependence' reported being 'in treatment'). Self-reported associations between drinking alcohol and the index crime were identified among two-fifths of respondents, rising to half of those reporting violent crimes. Conclusions To our knowledge, this is the first study to identify differing behaviours and needs among prisoners with high AUDIT score ranges, through additional analysis of individual questions. The study has identified high prevalence of alcohol use, varied problem behaviours, and links across drinking, crime and recidivism, supporting the argument for more extensive provision of alcohol-focused interventions in prisons. These should be carefully targeted based on initial screening and assessment, responsive, and include care pathways linking prisoners to community services. Finally, findings confirm the value and feasibility of routine use of the AUDIT screening tool in prison settings, to considerably enhance practice in the detection and understanding of alcohol problems, improving on current more limited questioning (e.g. 'yes or no' questions).

Abstract Background Colonoscopy is an invasive and costly procedure with a risk of serious complications. It would therefore be useful to prioritise colonoscopies by identifying people at higher risk of either cancer or premalignant adenomas. The aim of this study is to assess a model that identifies people with colorectal cancer, advanced, large and small adenomas. Methods Patients seen by gastroenterologists and colorectal surgeons between April 2004 and December 2006 completed a validated, structured self-administered questionnaire prior to colonoscopy. Information was collected on symptoms, demographics and medical history. Multinomial logistic regression was used to simultaneously assess factors associated with findings on colonoscopy of cancer, advanced adenomas and adenomas sized 6 -9 mm, and ≤ 5 mm. The area under the curve of ROC curve was used to assess the incremental gain of adding demographic variables, medical history and symptoms (in that order) to a base model that included only age. Results Sociodemographic variables, medical history and symptoms (from 8,204 patients) jointly provide good discrimination between colorectal cancer and no abnormality (AUC 0.83), but discriminate less well between adenomas and no abnormality (AUC advanced adenoma 0.70; other adenomas 0.67). Age is the dominant risk factor for cancer and adenomas of all sizes. Having a colonoscopy within the last 10 years confers protection for cancers and advanced adenomas. Conclusions Our models provide guidance about which factors can assist in identifying people at higher risk of disease using easily elicited information. This would allow colonoscopy to be prioritised for those for whom it would be of most benefit.

Abstract Background Cancer is a major cause of mortality and morbidity in patients with chronic kidney disease (CKD). In patients without kidney disease, screening is a major strategy for reducing the risk of cancer and improving the health outcomes for those who developed cancers by detecting treatable cancers at an early stage. Among those with CKD, the effectiveness, the efficacy and patients' preferences for cancer screening are unknown. Methods/Design This work describes the protocol for the DETECT study examining the effectiveness, efficiency and patient's perspectives of colorectal cancer screening using immunochemical faecal occult blood testing (iFOBT) for people with CKD. The aims of the DETECT study are 1) to determine the test performance characteristics of iFOBT screening in individuals with CKD, 2) to estimate the incremental costs and health benefits of iFOBT screening in CKD compared to no screening and 3) to elicit patients' perspective for colorectal cancer screening in the CKD population. Three different study designs will be used to explore the uncertainties surrounding colorectal cancer screening in CKD. A diagnostic test accuracy study of iFOBT screening will be conducted across all stages of CKD in patients ages 35-70. Using individually collected direct healthcare costs and outcomes from the diagnostic test accuracy study, cost-utility and cost-effective analyses will be performed to estimate the costs and health benefits of iFOBT screening in CKD. Qualitative in-depth interviews will be undertaken in a subset of participants from the diagnostic test accuracy study to investigate the perspectives, experiences, attitudes and beliefs about colorectal cancer screening among individuals with CKD. Discussion The DETECT study will target the three major unknowns about early cancer detection in CKD. Findings from our study will provide accurate and definitive estimates of screening efficacy and efficiency for colorectal cancer, and will allow better service planning and budgeting for early cancer detection in this at-risk population. The DETECT study is also registered with the Australia New Zealand Clinical Trials Registry ACTRN12611000538943

Abstract Background Bowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps. Methods We searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps) or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps. Results Colorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7) and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9). Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care) nor study type was associated with accuracy. Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies. Conclusions Current evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into account the limited value of symptoms.

Abstract Background Inhibitors of the kinase mTOR, such as rapamycin and everolimus, have been used as cancer therapeutics with limited success since some tumours are resistant. Efforts to establish predictive markers to allow selection of patients with tumours likely to respond have centred on determining phosphorylation states of mTOR or its targets 4E-BP1 and S6K in cancer cells. In an alternative approach we estimated eIF4E activity, a key effector of mTOR function, and tested the hypothesis that eIF4E activity predicts sensitivity to mTOR inhibition in cell lines and in breast tumours. Results We found a greater than three fold difference in sensitivity of representative colon, lung and breast cell lines to rapamycin. Using an assay to quantify influences of eIF4E on the translational efficiency specified by structured 5'UTRs, we showed that this estimate of eIF4E activity was a significant predictor of rapamycin sensitivity, with higher eIF4E activities indicative of enhanced sensitivity. Surprisingly, non-transformed cell lines were not less sensitive to rapamycin and did not have lower eIF4E activities than cancer lines, suggesting the mTOR/4E-BP1/eIF4E axis is deregulated in these non-transformed cells. In the context of clinical breast cancers, we estimated eIF4E activity by analysing expression of eIF4E and its functional regulators within tumour cells and combining these scores to reflect inhibitory and activating influences on eIF4E. Estimates of eIF4E activity in cancer biopsies taken at diagnosis did not predict sensitivity to 11-14 days of pre-operative everolimus treatment, as assessed by change in tumour cell proliferation from diagnosis to surgical excision. However, higher pre-treatment eIF4E activity was significantly associated with dramatic post-treatment changes in expression of eIF4E and 4E-binding proteins, suggesting that eIF4E is further deregulated in these tumours in response to mTOR inhibition. Conclusions Estimates of eIF4E activity predict sensitivity to mTOR inhibition in cell lines but breast tumours with high estimated eIF4E activity gain changes in eIF4E regulation in order to enhance resistance.