Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients. From an original observational study comprising 817 breast cancer patients, 99 women with operable breast cancer were retrospectively included in the present study. This cohort of patients were adjuvantly treated with tamoxifen, had provided serum samples suitable for measuring tamoxifen metabolites, and were relapse-free at 3 years after the primary treatment commenced. The median follow-up time from this entry point to breast cancer death was 13.9 years. Patients were CYP2D6 genotyped and grouped into four CYP2D6 phenotype groups (Ultra rapid, extensive, intermediate, and poor metabolizers). Tamoxifen and nine metabolites were quantified in serum (n = 86) and compared with CYP2D6 phenotype groups and outcome. Breast cancer patients with low concentrations of Z-4-hydroxy-tamoxifen (Z-4OHtam; ≤ 3.26 nM) had a breast cancer-specific survival (BCSS) of 60% compared to 84% in patients with Z-4OHtam concentrations > 3.26 nM (p = 0.020, log-rank hazard ratio (HR) = 3.56, 95% confidence interval (CI) = 1.14–11.07). For patients with Z-4-hydroxy-N-desmethyl-tamoxifen (Z-endoxifen) levels ≤ 9.00 nM BCSS was 57% compared to 84% for patients with concentrations > 9.00 nM (p = 0.029, HR = 3.73, 95% CI = 1.05–13.22). Low concentrations of Z-4OHtam and Z-endoxifen were associated with poorer survival also after adjusting for clinically relevant variables (HR = 4.27, 95% CI = 1.35–13.58, and HR = 3.70, 95% CI = 1.03–13.25, respectively). Overall survival analysis showed similar survival differences for both active metabolites. The Antiestrogen Activity Score showed comparable effects, but did not improve the prognostic information. Patients with Z-4OHtam and Z-endoxifen concentrations lower than 3.26 nM or 9.00 nM, respectively, showed an adverse outcome. Our results suggest that direct measurement of active tamoxifen metabolite concentrations could be of clinical value. Validation in larger study cohorts is warranted.

One of the factors that limits survival from out-of-hospital cardiac arrest is the interruption of chest compressions. During ventricular fibrillation and tachycardia the electrocardiogram reflects the probability of return of spontaneous circulation associated with defibrillation. We have used this in the current study to quantify in detail the effects of interrupting chest compressions.

Recently there has been interest in risk-adjusted cumulative sum charts, CUSUMs, to monitor the performance of e.g. hospitals, taking into account the heterogeneity of patients. Even though many outcomes involve time, only conventional regression models are commonly used. In this article we investigate how time to event models may be used for monitoring purposes. We consider monitoring using CUSUMs based on the partial likelihood ratio between an out-of-control state and an in-control state. We consider both proportional and non-proportional alternatives, as well as a head start. Against proportional alternatives, we present an analytic method of computing the expected number of observed events before stopping or the probability of stopping before a given observed number of events. In a stationary set-up, the former is roughly proportional to the average run length in calendar time. Adding a head start changes the threshold only slightly if the expected number of events until hitting is used as a criterion. However, it changes the threshold substantially if a false alarm probability is used. In simulation studies, charts based on survival analysis perform better than simpler monitoring schemes. We present one example from retail finance and one medical application.

Background: Assessment of heart rate (HR) is essential during newborn resuscitation, and comparison of dry-electrode ECG technology to standard monitoring by 3-lead ECG and Pulse Oximetry (PO) is lacking. Methods: NeoBeat, ECG, and PO were applied to newborns resuscitated at birth. Resuscitations were video recorded, and HR was registered every second. Results: Device placement time from birth was median (quartiles) 6 (4, 18) seconds for NeoBeat versus 138 (97, 181) seconds for ECG and 152 (103, 216) seconds for PO. Time to first HR presentation from birth was 22 (13, 45) seconds for NeoBeat versus 171 (129, 239) seconds for ECG and 270 (185, 357) seconds for PO. Proportion of time with HR feedback from NeoBeat during resuscitation from birth was 85 (69, 93)%, from arrival at the resuscitation table 98 (85, 100)%, and during positive pressure ventilation 100 (95, 100)%. For ECG, these proportions were, 25 (0, 43)%, 28 (0, 56)%, and 33 (0, 66)% and for PO, 0 (0, 16)%, 0 (0, 16)%, and 0 (0, 18)%. All p < 0.0001. Conclusions: NeoBeat was faster to place, presented HR more rapidly, and provided feedback on HR for a larger proportion of time during ongoing resuscitation compared to 3-lead ECG and PO.