Does early intensive multifactorial treatment reduce total cardiovascular burden in individuals with screen-detected diabetes? Findings from the ADDITION-Europe cluster-randomized trial.

AIMS: To describe the total cardiovascular burden (cardiovascular morbidity or mortality, revascularization or non-traumatic amputation) in individuals with screen-detected diabetes in the ADDITION-Europe trial and to quantify the impact of the intervention on multiple cardiovascular events over 5 years. METHODS: In a pragmatic, cluster-randomized, parallel-group trial in four centres (Denmark; Cambridge, UK; the Netherlands; and Leicester, UK), 343 general practices were randomized to screening plus routine care (n = 1379 patients), or screening and promotion of target-driven, intensive treatment of multiple risk factors (n = 1678). We estimated the effect of the intervention on multiple cardiovascular events after diagnosis of diabetes using the Wei, Lin and Weissfeld method. RESULTS: Over 5.3 years, 167 individuals had exactly one cardiovascular event, 53 exactly two events, and 18 three or more events. The incidence rates (95% CI) of first events and any event per 1000 person-years were 14.6 (12.8-16.6) and 20.4 (18.2-22.6), respectively. There were non-significant reductions in the risk of a first (hazard ratio 0.83, 95% CI 0.65-1.05) and second primary endpoint (hazard ratio 0.70, 95% CI 0.43-1.12). The overall average hazard ratio for any event was 0.77 (95% CI 0.58-1.02). CONCLUSIONS: Early intensive multifactorial treatment was not associated with a significant reduction in total cardiovascular burden at 5 years. Focusing on first events in cardiovascular disease prevention trials underestimates the total cardiovascular burden to patients and the health service.

Screening for type 2 diabetes. Lessons from the ADDITION-Europe study.

AIMS: To describe and compare attendance rates and the proportions of people identified with Type 2 diabetes mellitus in people with previously unknown diabetes who participated in screening programmes undertaken in general practice in the UK, Denmark and the Netherlands as part of the ADDITION-Europe study. METHODS: In Cambridge, routine computer data searches were conducted to identify individuals aged 40-69 years at high risk of Type 2 diabetes using the Cambridge Diabetes Risk Score. In Denmark, the Danish Diabetes Risk Score was mailed to individuals aged 40-69 years, or completed by patients visiting their general practitice. In the Netherlands, the Hoorn Symptom Risk Questionnaire was mailed to individuals aged 50-69 years. In these three centres, high-risk individuals were invited to attend subsequent steps in the screening programme, including random blood glucose, HbA(1c) , fasting blood glucose and/or oral glucose tolerance test. In Leicester, eligible people aged 40-69 years were invited directly for an oral glucose tolerance test. In all centres, Type 2 diabetes was defined according to World Health Organization 1999 diagnostic criteria. RESULTS: Attendance rates ranged from 20.2% (oral glucose tolerance test in Leicester without pre-stratification) to 95.1% (random blood glucose in opportunistic screening in Denmark in high-risk people). The percentage of people with newly detected Type 2 diabetes from the target population ranged from 0.33% (Leicester) to 1.09% (the Netherlands). CONCLUSIONS: Screening for Type 2 diabetes was acceptable and feasible, but relatively few participants were diagnosed in all participating centres. Different strategies may be required to increase initial attendance and ensure completion of screening programmes.

Diabetes Care Protocol: effects on patient-important outcomes. A cluster randomized, non-inferiority trial in primary care.

AIMS: The Diabetes Care Protocol (DCP) combines task delegation, intensification of diabetes treatment and feedback. It reduces cardiovascular risk in Type 2 diabetes (T2DM) patients. This study determines the effects of DCP on patient-important outcomes. METHODS: A cluster randomized, non-inferiority trial, by self-administered questionnaires in 55 Dutch primary care practices: 26 practices DCP (1699 patients), 26 usual care (1692 patients). T2DM patients treated by their general practitioner were included. Main outcome was the 1-year between-group difference in Diabetes Health Profile (DHP-18) total score. SECONDARY OUTCOMES: DHP-18 subscales, general perceived health [Medical Outcomes Study 36-Items Short Form Health Survey (SF-36), Euroqol 5 Dimensions (EQ-5D) and Euroqol visual analogue scale (EQ-VAS)], treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire; DTSQ status) and psychosocial self-efficacy (Diabetes Empowerment Scale Short Form; DES-SF). Per protocol (PP) and intention-to-treat (ITT) analyses were performed: non-inferiority margin Delta=-2%. At baseline 2333 questionnaires were returned and 1437 1 year thereafter. RESULTS: Comparing DCP with usual care, DHP-18 total score was non-inferior: PP -0.88 (95% CI -1.94 to 0.12), ITT -0.439 (95% CI -1.01 to 0.08), SF-36 'health change' improved: PP 3.51 (95% CI 1.23 to 5.82), ITT 1.91 (95% CI 0.62 to 3.23), SF-36 'social functioning' was inconclusive: PP-1.57 (95% CI-4.3 to 0.72), ITT-1.031 (95% CI-2.52 to -0.25). Other DHP and SF-36 scores were inconsistent or non-inferior. DHP-18 'disinhibited eating' was significantly worse in PP analyses. For EQ-5D/EQ-VAS, DTSQ and DES-SF, no significant between-group differences were found. CONCLUSION: DCP does not seem to influence health status negatively, therefore diabetes care providers should not shrink from intensified treatment. However, they should take possible detrimental effects on 'social functioning' and 'disinhibited eating' into account.

Diagnostic accuracy for different strategies of image-guided breast intervention in cases of nonpalpable breast lesions.

To find out whether ultrasound-guided fine-needle aspiration (FNA) and ultrasound and stereotactic-guided large core needle biopsy (LCNB) are reliable alternatives to needle-localised open breast biopsy (NLBB) in daily practice, we performed a retrospective study and evaluated the validity of these methods. In all, 718 women with 749 nonpalpable breast lesions from three Dutch Hospitals were included, and the validity of the various methods for diagnosis was assessed. This was carried out according to a method described by Burbank and Parker for evaluating the quality of an image-guided breast intervention. We compared our results with the outcome of the COBRA study. Overall, all diagnostic strategies (NLBB, FNA, LCNB ultrasound and stereotactic guided) show comparable agreement rates. However, the miss rates differ: 2% for NLBB, 3% for COBRA (LCNB in study setting), 5% for FNA and 8-12% for LCNB in practice. Fine-needle aspiration was nonconclusive in 29%, and shows an overestimation for DCIS in 9%. The DCIS underestimate rate in NLBB was 8%. For the assessment of lesions consisting of microcalcifications only and to exclude malignancy in all other lesions, a 14-gauge needle should be used. Ultrasound-guided intervention can be performed in a large percentage of nonpalpable lesions. Lesions consisting only of microcalcifications on mammography need special attention.

Diagnostic strategies in non-palpable breast lesions.

The number of non-palpable breast lesions is growing. Needle-localised breast biopsy (NLBB) is the gold standard for evaluating these lesions. Cost-saving techniques and less invasive alternatives such as core-needle biopsy (LCNB) and fine-needle aspiration (FNA) have emerged. The aim of this study was to find out if the lesions of patients who were sent directly for surgery to undergo a NLBB differed from lesions of patients who were send for a non-operative procedure. Furthermore, if a benign result was obtained, we assessed the total and kind of subsequent diagnostic procedures that were undertaken. A retrospective study on 718 women with 749 non-palpable breast lesions was performed. In 58% of women with non-palpable breast lesion, a non-surgical procedure was chosen. Lesions sent directly for surgery were more frequently not visible on ultrasound (62%) and mainly consisted of microcalcifications only (56%). In 45%, this primary surgical approach could have been avoided. If the non-operative procedure showed a non-malignant result, 41% of these women received an additional surgical diagnostic procedure. These figures obtained from routine daily practice show the importance of protocols in order to standardise diagnostic procedures and prevent unnecessary surgery.

The association between induced and spontaneous abortion and risk of breast cancer in Slovenian women aged 25-54.

The risk of breast cancer may be increased by induced or spontaneous abortion. The evidence for this association was evaluated in a population based case-control study in Slovenia, where 624 women aged 25-54 years with breast cancer diagnosed during 1988-1990 were matched for age and site of residence with controls randomly selected from the Slovenian Population Registry. Odds ratios (OR) and 95% confidence intervals (CI) were obtained by conditional logistic regression analyses. Spontaneous abortion was not associated with a significantly increased risk of breast cancer (nulliparous women: OR=1.41, 95% CI 0.22-9.01; uniparous women: OR=0.98, 95% CI 0.50-1.91; women with parity 2 or more: OR=1.40, 95% CI 0.91-2.15). Induced abortion was not associated with a statistically significant elevated risk. The risk of breast cancer was higher in nulliparous women (OR=2.49, 95% Cl 0.68-9.09), and was less among women who had more deliveries. In uniparous women, the risk of breast cancer appeared higher when the induced abortion took place before a first full-term pregnancy (OR=1.94, 95% CI 0.70-5.39) rather than after a first full-term pregnancy (OR=1.22, 95% CI 0.71-2.10) but neither of these odds ratios reached significance. We found no significant association between spontaneous abortion or induced abortion and breast cancer risk. This study found an elevated, but not statistically significant, risk associated with induced abortion among nulliparous women and among parous women when the induced abortion was before the first full-term pregnancy.