Dealing with unexpected manufacturing events: Can Decision Support Systems improve operators’performance by decreasing stress and workload?

The modern manufacturing environment is very stressful for operators in charge of the production process. Unexpected events may deteriorate the operators’ performance by increasing their mental stress and workload. To overcome this phenomenon, several production scheduling and rescheduling tools have been developed. Nowadays, these decision support systems (DSS) are assumed to reduce operators’ workload because they automatically reschedule the production planning. However, findings from the literature remain equivocal. Indeed, the effect of DSS has only been reported at a subjective level and in the absence of disruptions. Given that the modern manufacturing environment is increasingly using DSS to help operators in their decisions, it is important to understand if workload can really explain the drop in operators’ performances and how they could be improved by DSS. We performed a semi-systematic literature review on six databases (PsycInfo, PsycArticles, IEEE explore, Pubmed, Google Scholar, and Web of science) regarding the effect of DSS on operators’ performance and workload. This literature review underlines the lack of research on this specific research question. As an opening, we propose a neuroergonomic experimental protocol designed to investigate this question of particular interest in rescheduling tasks. This innovative and new protocol is programmed using Matlab. Participants have to schedule the production planning (e.g. 15 tasks) on a limited number of resources (e.g. 5 machines). In some trials, unexpected events such as the unavailability of a resource may occur. As a result, participants have to reschedule all the production planning. In some of the trials, they can use the help of the decision support system that instantly proposes a new production schedule, whereas in the remaining trials they can’t use it. Workload and stress are evaluated using subjective measures (e.g. the NASA-TLX for workload, and the Perceived Stress Scale for stress), behavioral ones (e.g. accuracy and response time) as well as physiological ones (i.e. electroencephalography - EEG - and electrocardiography - ECG). This study paves the way towards developing the neuroergonomic approach on DSS use and the manufacturing environment

Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study

Breast cancer; Pharmacogenomics; Tumour biomarkersCáncer de mama; Farmacogenómica; Biomarcadores tumoralesCàncer de mama; Farmacogenòmica; Biomarcadors tumoralsThese analyses explore the impact of homologous recombination repair gene mutations, including BRCA1/2 mutations and homologous recombination deficiency (HRD), on the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor talazoparib in the open-label, two-cohort, Phase 2 ABRAZO trial in germline BRCA1/2-mutation carriers. In the evaluable intent-to-treat population (N = 60), 58 (97%) patients harbor ≥1 BRCA1/2 mutation(s) in tumor sequencing, with 95% (53/56) concordance between germline and tumor mutations, and 85% (40/47) of evaluable patients have BRCA locus loss of heterozygosity indicating HRD. The most prevalent non-BRCA tumor mutations are TP53 in patients with BRCA1 mutations and PIK3CA in patients with BRCA2 mutations. BRCA1- or BRCA2-mutated tumors show comparable clinical benefit within cohorts. While low patient numbers preclude correlations between HRD and efficacy, germline BRCA1/2 mutation detection from tumor-only sequencing shows high sensitivity and non-BRCA genetic/genomic events do not appear to influence talazoparib sensitivity in the ABRAZO trial.In Manchester, this trial was undertaken in/supported by the NIHR Manchester Clinical Research Facility at The Christie Hospital NHS Foundation Trust. The ABRAZO study was sponsored by Medivation, which was acquired by Pfizer in September 2016 (grant number not applicable). The authors wish to thank Masaki Mihaila and the Pfizer clinical programming team for the ABRAZO correlative analyses. Medical writing support was provided by Dominic James, PhD, and Hannah Logan, PhD, of CMC AFFINITY, a division of IPG Health Medical Communications, and was funded by Pfizer

Scheduling and Rescheduling Operations Using Decision Support Systems: Insights From Emotional Influences on Decision-Making

For many years, manufacturers have focused on improving their productivity. Production scheduling operations are critical for this objective. However, in modern manufacturing systems, the original schedule must be regularly updated as it takes places in a dynamic and uncertain environment. The modern manufacturing environment is therefore very stressful for the managers in charge of the production process because they have to cope with many disruptions and uncertainties. To help them in their decision-making process, several decision support systems (DSSs) have been developed. A recent and enormous challenge is the implementation of DSSs to efficiently manage the aforementioned issues. Nowadays, these DSSs are assumed to reduce the users' stress and workload because they automatically (re)schedule the production by applying algorithms. However, to the best of our knowledge, the reciprocal influence of users' mental state (i.e., cognitive and affective states) and the use of these DSSs have received limited attention in the literature. Particularly, the influence of users' unrelated emotions has received even less attention. However, these influences are of particular interest because they can account for explaining the efficiency of DSSs, especially in modulating DSS feedback processing. As a result, we assumed that investigating the reciprocal influences of DSSs and users' mental states could provide useful avenues of investigation. The intention of this article is then to provide recommendations for future research on scheduling and rescheduling operations by suggesting the investigation of users' mental state and encouraging to conduct such research within the neuroergonomic approach

Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician’s choice: Results from the randomised phase III BEACON trial

Background: Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician’s choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL. Patients and methods: HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m2 every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (≥5 points) in HRQoL scores were compared. Results: Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P < 0.02); numerical improvement was reported in other functional scales. The findings from HRQoL symptom scales were consistent with adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of −9.4 and −10.8 points, respectively. Conclusion: There was evidence of benefit associated with etirinotecan pegol compared with current standard of care agents in multiple HRQoL measurements, including global health status and physical functioning, despite worse gastrointestinal symptoms (e.g. diarrhoea). Patients in both arms had a decline in HRQoL at disease progression. Study number: NCT01492101

Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial.

Background Talazoparib (1 mg/day) exhibited promising efficacy and safety in patients with advanced breast cancer during ABRAZO (NCT02034916); this study evaluated patient-reported outcomes (PROs).Patients and methods ABRAZO is a two-cohort, two-stage, phase 2 study of talazoparib in patients with advanced breast cancer after a response to prior platinum-based therapy (cohort 1 [C1], n = 49) or ≥3 platinum-free cytotoxic-based regimens (cohort 2 [C2], n = 35). PROs were assessed on day 1 (baseline), every 6 weeks for an initial 24 weeks, and every 12 weeks thereafter until progression, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and its breast cancer module, QLQ-BR23.Results Global health status/quality of life (GHS/QoL) was maintained from baseline across all time points for both C1 and C2. For C1 and C2, median time to deterioration (TTD) of GHS/QoL (95% confidence interval [CI]) was 2.8 (2.1, 3.0) and 5.5 (4.2, 5.7) months, respectively. Median TTD for all QLQ-C30 functional scales for C1 and C2 ranged 2.1-3.1 months and 4.2-5.6 months, respectively; median TTD for all QLQ-BR23 symptom scales ranged 2.6-4.0 months and 4.2-5.6 months, respectively. There were no statistically significant differences in estimated overall change from baseline in the GHS/QoL scale for both cohorts (C1: -2.6 [95% CI, -7.8, 2.5]; C2: 1.2 [95% CI, -5.5, 8.0]). Significant overall improvements in the breast symptoms and arm symptoms and the future perspective of patients in C1 and C2 were observed, despite the statistically significant and clinically meaningful overall deterioration among patients regarding their role functioning (in C1) and dyspnoea symptoms (in C2).Conclusion Despite the statistically significant and clinically meaningful overall deterioration among patients regarding their role functioning (in C1) and dyspnoea symptoms (in C2), patients in both C1 and C2 reported significant overall improvements in their breast symptoms, arm symptoms and future perspective, and their GHS/QoL was maintained from baseline

A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO).

PURPOSE:To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer. PATIENTS AND METHODS:ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. RESULTS:We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31-75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10-35; cohort 1] and 37% [95% CI, 22-55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC), and 29% (hormone receptor-positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval 6 months). CONCLUSIONS:Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation