1 The objective of this double-blind parallel-group study was to compare the tolerability of isradipine and amlodipine, specifically, the side-effects known to be related to the use of dihydropyridine calcium antagonists. 2 A total of 205 patients with mild-to-moderate essential hypertension were randomized to receive either the sustained-release (SRO) formulation of isradipine (n = 103) or amlodipine (n = 102), both at dosages of 5 mg once daily. Blood pressure measurements were taken at the end of the dosing interval to assess the antihypertensive efficacy of the two drugs. 3 Adverse reactions were assessed in two ways: a) spontaneously reported adverse events were recorded and investigated in depth for severity, duration, relation to the study drug, and outcome; b) a questionnaire was used to elicit specific adverse reactions known to be related to the use of dihydropyridine calcium antagonists which were evaluated for severity, duration, relation to the study drug, and outcome.4 After 6 weeks of active treatment, both isradipine and amlodipine reduced mean sitting systolic/diastolic blood pressure: from 165.1/100.1 to 145.2/89.7 mm Hg with isradipine; and from 164.1/100.6 to 145.7/90.5 mm Hg with amlodipine. There was no difference in antihypertensive effect between isradipine and amlodipine (95% CI: -3.73 to 4.73 and -1.89 to 3.49 for differences in systolic and diastolic blood pressure, respectively). 5 The number of patients spontaneously reporting adverse events was significantly higher (P = 0.02; 95% CI: 3.1 to 26.7%) with amlodipine (33.3%) than with isradipine (18.4%). 6 The incidence of spontaneously reported ankle oedema was statistically significantly greater with amlodipine than with isradipine (14.7% vs 5.8%, respectively, P = 0.04). In addition, the severity (P = 0.02) and duration (P = 0.03) of the ankle oedema was greater with amlodipine than with isradipine. Moreover, eight patients taking amlodipine discontinued treatment due to this side-effect compared with none of the patients taking isradipine. 7 By questionnaire, the severity (P = 0.03) and duration (P = 0.02) of nausea as well as the severity of ankle oedema (P = 0.04) were greater with amlodipine than with isradipine.

Patients' MMSE and ADL scores confirmed the meta-analyses of rivastigmine efficacy trials, while NPI scores exceeded efficacy results. Proportionately more patients responded to (titrated) treatment than in fixed-dose RCTs. Caregivers reported less burden (similar to meta-analysis) and better general health over the study period. Where efficacy and effectiveness results diverge, the benefit is in 'real-world' effectiveness. Large sample, multi-country replications, less sensitive to censoring secondary to missing data and powered to permit advanced modeling, as well as RCTs with adaptive designs to accommodate titration, are needed. The profile of patients most likely to benefit from treatment or most vulnerable to treatment outcome must be studied, as must the impact of physician- and center-related variables on outcomes.

Background Registration and coding of cause of death is prone to error since determining the exact underlying condition leading directly to death is challenging. In this study, causes of death from the death certificates were compared to patients’ medical files interpreted by experts at University Hospitals Leuven (UHL), to assess concordance between sources and its impact on cancer survival assessment. Methods Breast cancer patients treated at UHL (2009–2014) (follow-up until December 31st 2016) were included in this study. Cause of death was obtained from death certificates and expert-reviewed medical files at UHL. Agreement was calculated using Cohen’s kappa coefficient. Cause-specific survival (CSS) was calculated using the Kaplan-Meier method and the relative survival probability (RS) using the Ederer II and Pohar Perme method. Results A total of 2862 patients, of whom 354 died, were included. We found an agreement of 84.7% (kappa-value of 0.69 (95% C.I.: 0.62–0.77)) between death certificates and medical files. Death certificates had 10.7% false positive and 4.5% false negative rates. However, five-year CSS and RS measures were comparable for both sources. Conclusion For breast cancer patients included in our study, fair agreement of cause of death was seen between death certificates and medical files with similar CSS and RS estimations.

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Background The Regan Composite Risk Score (RCRS) is a web-based prognostic and predictive calculator to guide the use of adjuvant exemestane plus ovarian function suppression (AI + OFS) versus tamoxifen plus ovarian function suppression (TAM + OFS) or tamoxifen alone (TAM) for premenopausal women with hormone receptor-positive HER2-negative early breast cancer (HR+/HER2- EBC). We compared our adjuvant endocrine therapy policy based on the tumor board with the treatment guided by the RCRS during 2 time periods, one before and one after the acquaintance of the Tamoxifen and Exemestane Trial (TEXT) and Suppression and Ovarian Function Trial (SOFT) data. This allowed us to see a possible evolution in therapy policy. Methods A retrospective cohort study of 563 premenopausal patients with HR+/HER2- and HER2+ EBC diagnosed at the University Hospital of Leuven during 2 periods, 2010-2012 (cohort 1) and 2015-2017 (cohort 2), was conducted. For each patient with HER2- EBC, the RCRS was calculated by entering the requested characteristics in the online available tool. The primary outcome was to investigate how frequent our therapy differed from the therapy guided by the RCRS based on the estimated 8-yr distant relapse free interval (DRFI) with an arbitrary cut-off set at 3 %. If the received therapy was ≥ 3 % less efficient in 8-year DRFI compared to the optimal therapy according to RCRS, the patient was considered undertreated. If the received therapy differed by less than 3 % in 8-year DRFI compared to the optimal therapy according to RCRS and yet the most intensive therapy (AI + OFS > TAM + OFS > TAM) was administered, the patient was considered overtreated. In the other cases, the patient was considered to have been treated concordant with the RCRS. Secondarily, nonadherence of the HER2- and HER2+ patients towards the endocrine treatments leading to therapy switch because of intolerance was recorded at 6, 12, 24 and 36 months. Analyses were performed using SAS software and the comparison of both cohorts was performed by the chi-squared test for categorical variables. Results According to the RCRS, 43.2 % (89/206) of the HER2-negative patients of cohort 1 were undertreated compared to 22.1 % (43/194) in cohort 2 (chi- squared test, p-value < 0.001). The number of overtreated patients also differed significantly between the two cohorts (chi-squared test, p-value = 0.003) with 2.9 % (6/206) in the first cohort and 10.3 % (20/194) in the second cohort. Finally, the number of patients treated concordant with the guidance derived from the RCRS was 53.9 % (111/206) in cohort 1 and 67.5 % (131/194) in cohort 2 (chi-squared test, p-value = 0.005). Treatment intolerance and switch was observed in 34.8 %, 16.7 % and 12.4 % of the patients receiving AI + OFS, TAM + OFS or TAM as initial therapy respectively; this was numerically higher for all treatments in cohort 2 vs cohort 1, although the observed difference was only significant for TAM. Conclusion In our center, a recent cohort of premenopausal women was more likely to be treated with the adjuvant endocrine treatment concordant with the guidance derived from the RCRS when using an arbitrary cut-off of 3 % to define a relevant improvement in outcome. Citation Format: Charlotte Berteloot, Patrick Neven, Maja Vangoitsenhoven, Annouschka Laenen, Hans Wildiers, Kevin Punie, Ann Smeets, Ines Nevelsteen, Sileny Han, Thaïs Baert, Hilde Janssen, Eva Oldenburger, Adinda Baten, Patrick Berteloot, Rani Vanhoudt, Anne Deblander, Chantal Remmeriev, Christine Desmedt. Real world adjuvant endocrine treatment in premenopausal breast cancer patients compared with the proposed algorithm using the Regan Composite Risk Score [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-02-04.