Subjective Versus Objective Outcomes of Antipsychotics for the Treatment of Neuropsychiatric Symptoms Associated with Dementia.

BACKGROUND: Knowledge about treatment status can influence effects measured in trials when subjective scales are used. OBJECTIVE: The aim of this study was to compare subjective outcomes with objective outcomes of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia. METHODS: We performed a meta-epidemiological study of 38 randomized, placebo-controlled trials. For effectiveness, we used change in NPS and response rate as subjective outcomes, while overall dropout and additional psychotropic use were used as objective outcomes. For side effects, extrapyramidal symptoms (EPS) and somnolence were used as subjective outcomes, while dropout due to adverse events, medication use for EPS, and participants falling were used as objective outcomes. RESULTS: Conventional antipsychotics reduced NPS more than placebo (standardized mean difference [SMD] - 0.36, 95% confidence interval [CI] - 0.49 to - 0.23), as did atypical antipsychotics (SMD - 0.14, 95% CI - 0.19 to - 0.08). Response rates in the drug groups were also higher. Overall dropout did not differ between conventional antipsychotics and placebo (odds ratio [OR] 1.03, 95% CI 0.77-1.37) or atypical antipsychotics and placebo (OR 1.01, 95% CI 0.89-1.14). Furthermore, additional psychotropic use did not differ. The risk of EPS was higher for conventional (OR 2.93, 95% CI 2.04-4.22) and atypical antipsychotics (OR 1.52, 95% CI 1.23-1.88) versus placebo, as was the risk of somnolence and dropout due to adverse events, but medication use for EPS, as well as risk of falls, was not. CONCLUSIONS: The effectiveness of antipsychotics for NPS in dementia based on subjective scales was not confirmed using objective outcomes, in contrast to the increased risk of side effects.

Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients.

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events.

Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: an observational study.

PURPOSE: The primary aim was to study the risk of cardiovascular mortality in patients with differentiated thyroid carcinoma (DTC). Secondary aims were to evaluate all-cause mortality and explore the relation between thyroid-stimulating hormone (TSH; also known as thyrotropin) level and these outcome parameters. PATIENTS AND METHODS: Subjects from two cohorts were retrospectively compared by Cox regression analyses; 524 patients with DTC and 1,572 sex- and age-matched controls from a large population-based study in the same geographic region. RESULTS: Mean age plus or minus standard deviation was 49 ± 14 years. Median follow-up was 8.5 years (interquartile range [IQR], 4.1 to 15.9 years) for patients with DTC and 10.5 years (IQR, 9.9 to 10.9 years) for controls. One hundred patients with DTC (19.1%) died, 22 (4.2%) as a result of cardiovascular disease, 39 (7.4%) as a result of DTC, and 39 (7.4%) as a result of other/unknown causes. Eighty-five controls (5.4%) died, 24 (1.5%) as a result of cardiovascular disease and 61 (3.9%) as a result of other/unknown causes. Patients with DTC had an increased risk of cardiovascular and all-cause mortality (hazard ratios [HRs], 3.35 [95% CI, 1.66 to 6.74] and 4.40 [95% CI, 3.15 to 6.14], respectively, adjusted for age, sex, and cardiovascular risk factors). Within the DTC group, TSH level was predictive for cardiovascular mortality; the adjusted HR was 3.08 (95% CI, 1.32 to 7.21) for each 10-fold decrease in geometric mean TSH level. CONCLUSION: The risk of cardiovascular and all-cause mortality is increased in patients with DTC, independent of age, sex, and cardiovascular risk factors. A lower TSH level is associated with increased cardiovascular mortality, supporting the current European Thyroid Association and the American Thyroid Association guidelines of tempering TSH suppression in patients with low risk of cancer recurrence. Furthermore, patients with DTC may benefit from assessment and treatment of cardiovascular risk factors.

Five year outcomes of hypofractionated simultaneous integrated boost irradiation in breast conserving therapy; patterns of recurrence.

In 2005, we introduced hypofractionated 3-dimensional conformal radiotherapy with a simultaneous integrated boost (3D-CRT-SIB) technique after breast conserving surgery. In a consecutive series of 752 consecutive female invasive breast cancer patients (stages I-III) the 5-year actuarial rate for local control was 98.9%. This new technique gives excellent 5-year local control.