Cambridge Trial Research Articles

Modification of cardiovascular disease risk by health behaviour change following type 2 diabetes diagnosis.

Among adults with type 2 diabetes (T2D), unhealthy behaviours are associated with increased risk of cardiovascular disease (CVD) events. To date, little research has considered whether healthy changes in behaviours following T2D diagnosis reduce CVD risk. A cohort of 867 adults with screen-detected T2D, participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge trial, were followed for 10years for incidence of CVD events. Diet, alcohol consumption, moderate/vigorous physical activity and smoking were assessed by questionnaire at the time of T2D screening and 1year later. We estimated associations between health behaviours and CVD using Cox regression. We assessed modification of the associations by behaviour change in the year following T2D diagnosis. Smoking [hazard ratio (HR): 1.73 (95% CI: 1.04, 2.87)] and high fat intake [HR: 1.70 (95% CI: 1.02, 2.85)] were associated with a higher hazard of CVD, while high plasma vitamin C [HR: 0.44 (95% CI: 0.22, 0.87)] and high fibre intake [HR: 0.60 (95% CI: 0.36, 0.99)] were associated with a lower hazard of CVD. Reduction in fat intake following T2D diagnosis modified associations with CVD. In particular, among those with the highest fat intake, decreasing intake attenuated the association with CVD [HR: 0.75 (95% CI: 0.36, 1.56)]. Following T2D diagnosis, decreasing fat intake was associated with lower long-term CVD risk. This evidence may raise concerns about low-carbohydrate, high-fat diets to achieve weight loss following T2D diagnosis. Further research considering the sources of fat is needed to inform dietary recommendations. This trial is registered as ISRCTN86769081. Retrospectively registered on 15 December 2006.

Association Between Primary Care Practitioner Empathy and Risk of Cardiovascular Events and All-Cause Mortality Among Patients With Type 2 Diabetes: A Population-Based Prospective Cohort Study.

To examine the association between primary care practitioner (physician and nurse) empathy and incidence of cardiovascular disease (CVD) events and all-cause mortality among patients with type 2 diabetes. This was a population-based prospective cohort study of 49 general practices in East Anglia (United Kingdom). The study population included 867 individuals with screen-detected type 2 diabetes who were followed up for an average of 10 years until December 31, 2014 in the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care (ADDITION)-Cambridge trial. Twelve months after diagnosis, patients assessed practitioner empathy and their experiences of diabetes care during the preceding year using the consultation and relational empathy (CARE) measure questionnaire. CARE scores were grouped into tertiles. The main outcome measures were first recorded CVD event (a composite of myocardial infarction, revascularization, nontraumatic amputation, stroke, and fatal CVD event) and all-cause mortality, obtained from electronic searches of the general practitioner record, national registries, and hospital records. Hazard ratios (HRs) were estimated using Cox models adjusted for relevant confounders. The ADDITION-Cambridge trial is registered as ISRCTN86769081. Of the 628 participants with a completed CARE score, 120 (19%) experienced a CVD event, and 132 (21%) died during follow up. In the multivariable model, compared with the lowest tertile, higher empathy scores were associated with a lower risk of CVD events (although this did not achieve statistical significance) and a lower risk of all-cause mortality (HRs for the middle and highest tertiles, respectively: 0.49; 95% CI, 0.27-0.88, P = .01 and 0.60; 95% CI, 0.35-1.04, P = .05). Positive patient experiences of practitioner empathy in the year after diagnosis of type 2 diabetes may be associated with beneficial long-term clinical outcomes. Further work is needed to understand which aspects of patient perceptions of empathy might influence health outcomes and how to incorporate this understanding into the education and training of practitioners.

How good are GPs at adhering to a pragmatic trial protocol in primary care? Results from the ADDITION-Cambridge cluster-randomised pragmatic trial

ObjectiveTo assess the fidelity of general practitioners’ (GPs) adherence to a long-term pragmatic trial protocol.DesignRetrospective analyses of electronic primary care records of participants in the pragmatic cluster-randomised ADDITION (Anglo-Danish-Dutch Study...

Leading an Experiment in Police Body-Worn Video Cameras

Body-worn video (BWV) is seen internationally as having the potential to reduce public complaints against police, police use of force, and attrition of prosecutions due to lack of physical evidence. Beyond the Cambridge trial in Rialto, California, however, no studies have tested the effects of BWV. The present study documents a Police leaders’ implementation of a randomized controlled trial of the use of BWV. The main objectives are to identify the challenges to implementing a trial and identify how they were overcome. The solutions to these challenges may provide key lessons for police leaders, not only as they undertake evidence-based testing, but also as they manage police operations and implement change.

Changes in diet, cardiovascular risk factors and modelled cardiovascular risk following diagnosis of diabetes: 1‐year results from the ADDITION‐Cambridge trial cohort

AimsTo describe change in self-reported diet and plasma vitamin C, and to examine associations between change in diet and cardiovascular disease risk factors and modelled 10-year cardiovascular disease risk in the year following diagnosis of Type 2 diabetes.MethodsEight hundred and sixty-seven individuals with screen-detected diabetes underwent assessment of self-reported diet, plasma vitamin C, cardiovascular disease risk factors and modelled cardiovascular disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial. Multivariable linear regression was used to quantify the association between change in diet and cardiovascular disease risk at 1 year, adjusting for change in physical activity and cardio-protective medication.ResultsParticipants reported significant reductions in energy, fat and sodium intake, and increases in fruit, vegetable and fibre intake over 1 year. The reduction in energy was equivalent to an average-sized chocolate bar; the increase in fruit was equal to one plum per day. There was a small increase in plasma vitamin C levels. Increases in fruit intake and plasma vitamin C were associated with small reductions in anthropometric and metabolic risk factors. Increased vegetable intake was associated with an increase in BMI and waist circumference. Reductions in fat, energy and sodium intake were associated with reduction in HbA1c, waist circumference and total cholesterol/modelled cardiovascular disease risk, respectively.ConclusionsImprovements in dietary behaviour in this screen-detected population were associated with small reductions in cardiovascular disease risk, independently of change in cardio-protective medication and physical activity. Dietary change may have a role to play in the reduction of cardiovascular disease risk following diagnosis of diabetes.

Normal tissue complication probability (NTCP) parameters for breast fibrosis: Pooled results from two randomised trials

IntroductionThe dose–volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. Materials and methodsWe pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n=1410) were used to test the predicted models. Results26.8% patients in the Cambridge trial (5years) and 20.7% patients in the EORTC trial (10years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4Gy, γ50=0.9 and n=0.011 for the Niemierko model and BEUD3(50)=132Gy, m=0.35 and n=0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. ConclusionsThis large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter ‘n’ does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis.

Proteolytic Cleavage of the CD44 Adhesion Molecule in Multiple Human Tumors

Cell surface adhesion molecules are crucial for the development and/or pathogenesis of various diseases including cancer. CD44 has received much interest as a major adhesion molecule that is involved in tumor progression. We have previously demonstrated that the ectodomain of CD44 undergoes proteolytic cleavage by membrane-associated metalloproteases in various tumor cell lines. The remaining membrane-bound CD44 cleavage product can be detected using antibodies against the cytoplasmic domain of CD44 (anti-CD44cyto antibody). However, the cleavage of CD44 in primary human tumors has not been investigated. Using Western blots with anti-CD44cyto antibody to assay human tumor tissues, we show that the CD44 cleavage product can be detected in 58% (42 of 72) of gliomas but not in normal brain. Enhanced CD44 cleavage was also found in 67% (28 of 42) of breast carcinomas, 45% (5 of 11) of non-small cell lung carcinomas, 90% (9 of 10) of colon carcinomas, and 25% (3 of 12) of ovarian carcinomas. Tumors expressing a CD44 splice variant showed a significantly higher incidence of enhanced CD44 cleavage. The wide prevalence of CD44 cleavage suggests that it plays an important role in the pathogenesis of human tumors.

The superhighway in action: the Cambridge trial

UK companies are at the forefront of world efforts to bring the communications revolution to the home. The author describes a comprehensive ATM-based trial currently running in the UK. The first phase of the trial was set up to solve the technical issues involved in setting up and operating a low cost, fully switched ATM-end-to-end infrastructure capable of delivering a wide range of information types, up to and including video. It also explored the basic logistics of service provision, including for example, a regularly updated news-on-demand service. The second phase extends the number of users and implements some cost reductions in the technology employed, but also focuses on the development of services. For this expansion of the trial an environment has been created (the `Service Nursery') for development and trialling of the new generation of multimedia services that will make the superhighway a commercial reality.

TREATMENT OF APPARENTLY EARLY BREAST CANCER 2. WHERE WE ARE GOING

The results of various methods of treatment of breast cancer and the direction in which they are leading are examined. Methods vary from superradical mastectomy to local excision of the lump from the breast with or without postoperative radiotherapy to the chest wall or lymph nodes. In uncontrolled trials the methods have produced similar results regardless of lymph node involvement. A variety of controlled trials are not proceeding: the Manchester trial the National Surgical Adjuvant Breast Project the Copenhagen trial the Cambridge trial the Guys Hospital trial and the Edinburgh trial. Generally they have demonstrated no advantage for the more aggressive methods. In particular prophylactic postoperative radiotherapy to the chest wall or lymph nodes neither prolongs survival nor prevents metastases; delayed treatment of recurrence is as effective in the control of local disease avoiding unnecessary treatment and morbidity in other cases. The value of radical mastectomy is not yet settled although removal of the pectoral muscles and upper axillary nodes is probably unnecessary.