Effectiveness,safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real-world data from the noninterventional TACTIC study in Germany

The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.     

Quality and denoising in real‐time functional magnetic resonance imaging neurofeedback: A methods review

Neurofeedback training using real‐time functional magnetic resonance imaging (rtfMRI‐NF) allows subjects voluntary control of localised and distributed brain activity. It has sparked increased interest as a promising non‐invasive treatment option in neuropsychiatric and neurocognitive disorders, although its efficacy and clinical significance are yet to be determined. In this work, we present the first extensive review of acquisition, processing and quality control methods available to improve the quality of the neurofeedback signal. Furthermore, we investigate the state of denoising and quality control practices in 128 recently published rtfMRI‐NF studies. We found: (a) that less than a third of the studies reported implementing standard real‐time fMRI denoising steps, (b) significant room for improvement with regards to methods reporting and (c) the need for methodological studies quantifying and comparing the contribution of denoising steps to the neurofeedback signal quality. Advances in rtfMRI‐NF research depend on reproducibility of methods and results. Notably, a systematic effort is needed to build up evidence that disentangles the various mechanisms influencing neurofeedback effects. To this end, we recommend that future rtfMRI‐NF studies: (a) report implementation of a set of standard real‐time fMRI denoising steps according to a proposed COBIDAS‐style checklist ( https://osf.io/kjwhf/ ), (b) ensure the quality of the neurofeedback signal by calculating and reporting community‐informed quality metrics and applying offline control checks and (c) strive to adopt transparent principles in the form of methods and data sharing and support of open‐source rtfMRI‐NF software. Code and data for reproducibility, as well as an interactive environment to explore the study data, can be accessed at https://github.com/jsheunis/quality‐and‐denoising‐in‐rtfmri‐nf.     

Antiprotozoal activity of diterpenoids isolated from Zhumeria majdae- absolute configuration by circular dichroism

PurposeZhumeria majdae, a unique species of the Zhumeria genus, is an endemic Iranian plant in the Lamiaceae family. Phytochemical investigation and biological activity of this plant are rarely reported. The current study aimed to find new antiprotozoal compounds from the roots of Z. majdae and to determine the absolute configuration of isolated compounds by circular dichroism.MethodsThe extraction process from roots and aerial parts of Z. majdae was carried out by hexane, ethyl acetate and methanol followed by testing their antiprotozoal effects against Leishmania donovani, Trypanosoma brucei rhodesiense, T. cruzi, and Plasmodium falciparum, respectively. Structure elucidation was done using 1D and 2D NMR spectroscopy and HREIMS spectrometry. In addition, experimental and theoretical circular dichroism spectroscopy was used to establish absolute configuration.ResultsIn comparison with aerial parts, the hexane extract from roots showed superior activity against T. b. rhodesiense, L. donovani and P. falciparum with IC₅₀ values of 5.4, 1.6 and 2.1 μg/ml, respectively. From eight abietane-type diterpenoids identified in roots, six were reported for the first time in the genus Zhumeria. 11,14-dihydroxy-8,11,13-abietatrien-7-one (6) exhibited a promising biological activity against P. falciparum (IC₅₀ 8.65 μM), with a selectivity index (SI) of 4.6, and lanugon Q (8) showed an IC₅₀ value of 0.13 μM and SI of 15.4 against T. b. rhodesiense.ConclusionAltogether, according to the results, of 8 isolated compounds, dihydroxy-8,11,13-abietatrien-7-one (6) and lanugon Q (8) exhibited a promising activity against T. b. rhodesiense and P. falciparum. In conclusion, these compounds could be potential candidates for further analysis and may serve as lead compounds for the synthesis of antiprotozoal agents. Open in a separate windowGraphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00345-w) contains supplementary material, which is available to authorized users.     

Hospital costs of complications after a pancreatoduodenectomy

BackgroundA pancreatoduodenectomy (PD) is a highly advanced procedure associated with considerable post-operative complications and substantial costs. In this study the hospital costs associated with complications after PD were assessed.MethodsA retrospective cohort study was conducted on 100 consecutive patients who underwent a pylorus-preserving (PP)PD between January 2012 and July 2013. Per patient, all complications occurring during admission or in the 30-day period after discharge were documented. All hospital costs related to the (PP)PD were defined as the costs of all medical interventions and resources during the hospitalisation period as recorded by the electronic supply tracking system.ResultsThe median hospital costs ranged from €17 482 for a patient without complications to €55 623 for a patient with a post-operative haemorrhage. A post-operative haemorrhage was associated with a 39.6% increase in total hospital costs after adjusting for patient characteristics. Other factors significantly associated with an increase in total hospital costs were: the presence of a malignancy other than a pancreatic adenocarcinoma (29.4% cost increase), the severity grade of a complication (34.3–70.6% increase) and the presence of a post-operative infection (32.4% increase).ConclusionsThis study provides an in-depth analysis of hospital costs and identifies factors that are associated with substantial cost consequences of specific complications occurring after a PD.     

Pharmacy in transition: A work sampling study of community pharmacists using smartphone technology

Introduction

The nature of community pharmacy is changing, shifting from the preparation and distribution of medicines to the provision of cognitive pharmaceutical services (CPS); however, often the provision of traditional services leaves little time for innovative services. This study investigated the time community pharmacists spend on the tasks and activities of daily practice and to what extent they are able to implement CPS-related services in daily practice.