Clinical outcome data for symptomatic breast cancer: the breast cancer clinical outcome measures (BCCOM) project

Background: Data collection for screen-detected breast cancer in the UK is fully funded which has led to improvements in clinical practice. However data on symptomatic breast cancer are deficient, and the aim of this project was to monitor the current practice. Methods: A data set was designed together with surrogate outcome measures to reflect best practice. Data from cancer registries initially required the consent of clinicians, but in the third year anonymised data were available. Results: The quality of data improved but this varied by region and only a third of cases were validated by clinicians. Regional variations in mastectomy rates were identified and one third of patients who underwent conservative surgery for invasive breast cancer were not recorded as receiving radiotherapy. Conclusions: National data are essential to ensure that all patients receive appropriate treatment for breast cancer, but variations still exist in the UK and further improvement in data capture is required

Online self-assessment of cardiovascular risk using the Joint British Societies (JBS3)-derived heart age tool: a descriptive study.

OBJECTIVE: A modified version of the Joint British Societies (JBS3) 'heart age' tool was introduced online to broaden access to personalised risk assessment to the general population and encourage participation in the National Health Service (NHS) Health Check programme. This study reports on its early uptake and the profiles of those who used the self-assessment tool to determine their own cardiovascular risk. DESIGN: Observational, retrospective analysis of online tool use. SETTING: Between February and July 2015, user data collected from the NHS Choices website, where the tool was hosted, were analysed anonymously using standard analytic packages. RESULTS: The online tool landing page was viewed 1.4 million times in the first 5 months, with increased activity following limited media coverage. Of the 575 782 users completing the data journey with a valid 'heart age' result, their demographic and risk factor profiles broadly resembled the population of England, although both younger users and males (60%) were over-represented. Almost 50% and 79% did not know or enter their blood pressure or total cholesterol values, respectively. Estimated heart age was higher than chronological age for 79% of all users, and also for 69% of younger users under 40 years who are at low 10-year risk and not invited for NHS Health Checks. CONCLUSIONS: These data suggest a high level of public interest in self-assessment of cardiovascular risk when an easily understood metric is used, although a large number of users lack awareness of their own risk factors. The heart age tool was accessed by a group not easily reached by conventional approaches yet is at high cardiovascular risk and would benefit most from early and sustained risk reduction. These are both important opportunities for interventions to educate and empower the public to manage better their cardiovascular risk and promote population-level prevention

A population based study of variations in operation rates for breast cancer, of comorbidity and prognosis at diagnosis: Failure to operate for early breast cancer in older women

Background Older women are less likely to have surgery for operable breast cancer. This population-based study examines operation rates by age and identifies groups which present with early or late disease. Methods 37 000 cancer registrations for 2007 were combined with Hospital Episode Statistics comorbidity data for England. Operation rates were examined by age, ethnicity, deprivation, comorbidity, screen-detection, tumour size, grade and nodal status. Early and late presentation were correlated with Nottingham Prognostic Index (NPI) groups and tumour size. Results The proportion of women not having surgery increased from 7–10% at ages 35–69 to 82% from age 90. From age 70, the proportion not having surgery rose by an average of 3.1% per year of age. Women with a Charlson Comorbidity Index score of ?1 (which increased with age), with tumours >50 mm or who were node positive, were less likely to have surgery. Although women aged 70–79 were more likely to have larger tumours, their tumours were also more likely to have an excellent or good NPI (p < 0.001). Good prognosis tumours were more likely to be screen-detected, and less likely in women aged 0–39, the deprived and certain ethnic groups (p < 0.02). Conclusions From age 70 there is an increasing failure to operate for breast cancer. Younger women and certain ethnic groups presented with more advanced tumours. Older women had larger tumours which were otherwise of good prognosis, and this would not account for the failure to operate which may in part be related to comorbidity in this age group

Evaluation of the uptake and delivery of the NHS Health Check programme in England, using primary care data from 9.5 million people: a cross-sectional study.

OBJECTIVES: To describe the uptake and outputs of the National Health Service Health Check (NHSHC) programme in England. DESIGN: Observational study. SETTING: National primary care data extracted directly by NHS Digital from 90% of general practices (GP) in England. PARTICIPANTS: Individuals aged 40-74 years, invited to or completing a NHSHC between 2012 and 2017, defined using primary care Read codes. INTERVENTION: The NHSHC, a structured assessment of non-communicable disease risk factors and 10-year cardiovascular disease (CVD) risk, with recommendations for behavioural change support and therapeutic interventions. RESULTS: During the 5-year cycle, 9 694 979 individuals were offered an NHSHC and 5 102 758 (52.6%) took up the offer. There was geographical variation in uptake between local authorities across England ranging from 25.1% to 84.7%. Invitation methods changed over time to incorporate greater digitalisation, opportunistic delivery and delivery by third-party providers.The population offered an NHSHC resembled the English population in ethnicity and deprivation characteristics. Attendees were more likely to be older and women, but were similar in terms of ethnicity and deprivation, compared with non-attendees. Among attendees, risk factor prevalence reflected population survey estimates for England. Where a CVD risk score was documented, 25.9% had a 10-year CVD risk ≥10%, of which 20.3% were prescribed a statin. Advice, information and referrals were coded as delivered to over 2.5 million individuals identified to have risk factors. CONCLUSION: This national analysis of the NHSHC programme, using primary care data from over 9.5 million individuals offered a check, reveals an uptake rate of over 50% and no significant evidence of inequity by ethnicity or deprivation. To maximise the anticipated value of the NHSHC, we suggest continued action is needed to invite more eligible people for a check, reduce geographical variation in uptake, prioritise engagement with non-attendees and promote greater use of evidence-based interventions especially where risk is identified

The use of surgery in the treatment of ER+ early stage breast cancer in England: variation by time, age and patient characteristics

AIM: To assess whether the proportion of patients aged 70 and over with ER+ operable breast cancer in England who are treated with surgery has changed since 2002, and to determine whether age and individual level factors including tumour characteristics and co-morbidity influence treatment choice. METHODS: A retrospective cohort analysis of routinely collected cancer registration data from two English regions (West Midlands, Northern & Yorkshire) was carried out (n = 17,129). Trends in surgical use over time for different age groups were assessed graphically and with linear regression. Uni- and multivariable logistic regressions were used to assess the effects of age, comorbidity, deprivation and disease characteristics on treatment choice. Missing data was handled using multiple imputation. RESULTS: There is no evidence of a change in the proportion of patients treated surgically over time. The multivariable model shows that age remains an important predictor of whether or not a woman with ER+ operable breast cancer receives surgery after covariate adjustment (Odds ratio of surgery vs no surgery, 0.82 (per year over 70)). Co-morbidity, deprivation, symptomatic presentation, later stage at diagnosis and low grade are also associated with increased probability of non-surgical treatment. CONCLUSION: Contrary to current NICE guidance in England, age appears to be an important factor in the decision to treat operable ER+ breast cancer non-surgically. Further research is needed to assess the role of other age-related factors on treatment choice, and the effect that current practice has on survival and mortality from breast cancer for older women

Induction of transforming growth factor beta receptors following focal ischemia in the rat brain

Transforming growth factor-βs (TGF-βs) regulate cellular proliferation, differentiation, and survival. TGF-βs bind to type I (TGF-βRI) and II receptors (TGF-βRII), which are transmembrane kinase receptors, and an accessory type III receptor (TGF-βRIII). TGF-β may utilize another type I receptor, activin-like kinase receptor (Alk1). TGF-β is neuroprotective in the middle cerebral artery occlusion (MCAO) model of stroke. Recently, we reported the expression pattern of TGF-β1-3 after MCAO. To establish how TGF-βs exert their actions following MCAO, the present study describes the induction of TGF-βRI, RII, RIII and Alk1 at 24 h, 72 h and 1 mo after transient 1 h MCAO as well as following 24 h permanent MCAO using in situ hybridization histochemistry. In intact brain, only TGF-βRI had significant expression: neurons in cortical layer IV contained TGF-βRI. At 24 h after the occlusion, no TGF-β receptors showed induction. At 72 h following MCAO, all four types of TGF-β receptors were induced in the infarct area, while TGF-βRI and RII also appeared in the penumbra. Most cells with elevated TGF-βRI mRNA levels were microglia. TGF-βRII co-localized with both microglial and endothelial markers while TGF-βRIII and Alk1 were present predominantly in endothels. All four TGF-β receptors were induced within the lesion 1 mo after the occlusion. In particular, TGF-βRIII was further induced as compared to 72 h after MCAO. At this time point, TGF-βRIII signal was predominantly not associated with blood vessels suggesting its microglial location. These data suggest that TGF-β receptors are induced after MCAO in a timely and spatially regulated fashion. TGF-β receptor expression is preceded by increased TGF-β expression. TGF-βRI and RII are likely to be co-expressed in microglial cells while Alk1, TGF-βRII, and RIII in endothels within the infarct where TGF-β1 may be their ligand. At later time points, TGF-βRIII may also appear in glial cells to potentially affect signal transduction via TGF-βRI and RII

Role of the lesion scar in the response to damage and repair of the central nervous system

Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation