Modelling incremental benefits on complications rates when targeting lower HbA1c levels in people with Type 2 diabetes and cardiovascular disease.

AIM: Glucose-lowering interventions in Type 2 diabetes mellitus have demonstrated reductions in microvascular complications and modest reductions in macrovascular complications. However, the degree to which targeting different HbA1c reductions might reduce risk is unclear. METHODS: Participant-level data for Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) participants with established cardiovascular disease were used in a Type 2 diabetes-specific simulation model to quantify the likely impact of different HbA1c decrements on complication rates. Ten-year micro- and macrovascular rates were estimated with HbA1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%) while holding other risk factors constant at their baseline levels. Cumulative relative risk reductions for each outcome were derived for each HbA1c decrement. RESULTS: Of 5717 participants studied, 72.0% were men and 74.2% White European, with a mean (sd) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9) mmHg, LDL-cholesterol 2.3 (0.9) mmol/l, HDL-cholesterol 1.13 (0.3) mmol/l and median Type 2 diabetes duration 9.6 (5.1-15.6) years. Ten-year cumulative relative risk reductions for modelled HbA1c values of 75, 64, 53 and 42 mmol/mol, relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and 46.4% for diabetes-related ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation; and 13.6%, 25.4%, 36.0% and 44.7 for single-eye blindness. CONCLUSIONS: These simulated complication rates might help inform the degree to which complications might be reduced by targeting particular HbA1c reductions in Type 2 diabetes.

Factors influencing loco-regional relapse in older breast cancer patients treated with tumour resection and tamoxifen.

BACKGROUND: In breast cancer patients (≥70 years), tumour resection plus tamoxifen (T + T) has a higher loco-regional relapse (LR) rate than mastectomy. This study examines factors influencing local recurrence in these cases. METHODS: Clinical records of 71 patients aged ≥70 years, randomised to the T + T arm of 2 randomised trials were reviewed. Cox Proportional Hazards model was used to determine the most significant variables. RESULTS: After 15-years follow-up, LR relapse occurred in 29/71, of whom 5 had synchronous metastatic disease. Most tumours recurred in the index quadrant. Subsequently 21/24 patients with loco-regional recurrence only had salvage mastectomy. Three variables significantly predicted LR: lympho-vascular invasion (LVI) (HR [95% CI]: 11.18 [4.47, 27.95], p < 0.01), ER negative status (HR [95% CI]: 0.27 [0.10, 0.72] p = 0.01), and tumour necrosis (HR [95% CI]: 2.65 [1.10, 6.37], p = 0.03). Final margin status was not associated with LR. CONCLUSIONS: Tumour resection + Tamoxifen in older patients results in long-term local control in the majority with most loco-regional failures being salvageable. Risk factors for LR are lympho-vascular invasion, ER status and tumour necrosis. Negative tumour excision margins did not significantly change local outcome in the absence of radiotherapy. In these older patients LVI significantly reduced survival time.

What can be done about hot flushes after treatment for breast cancer?

Breast cancer survivors frequently experience severe hot flushes as a result of their treatment. This can adversely affect their quality of life, compliance with treatment and overall survival. To relieve vasomotor symptoms, a variety of drugs have been used including clonidine, gabapentin, selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Stellate ganglion block (SGB) has recently emerged as a new technique against hot flushes and preliminary studies report encouraging efficacy with minimal complications. Other approaches include various alternative treatments and, in a few cases, hormone replacement therapy (HRT). All randomized, controlled studies of drugs, hormone treatments and alternative therapies for vasomotor symptoms have been reviewed and efficacy and safety noted. Side-effects of current medical treatments frequently outweigh the benefits--leading many patients to discontinue the medications. Statistically significant differences between placebo and test agent may not translate into a meaningful subjective benefit. Desvenlafaxine looks promising as does SGB, despite its invasive nature. The favorable safety profile of SGB is confirmed through the long experience of SGB performed for other medical purposes. The majority of non-HRT treatments for hot flushes are little better than placebo but early results from randomized trials of desvenlafaxine and pilot studies of SGB suggest that it is worthwhile to test their efficacy specifically in breast cancer survivors.