Patient-centred communication and empathy are key enablers for patient-centred care. However, several studies suggest a downward trend regarding the empathic communication skills of physicians during ...medical residency. It is known that communication training can have a positive effect on patient-centred communication, empathy and relational skills. Training residents in patient-centred communication and empathy can be an opportunity to improve the patient-centred care. To evaluate the training a tri-focal perspective will be used.
A 3-day training was developed to improve residents' patient-centred communication and empathy skills at an academic medical health centre, in the Netherlands. The training included: (1) the basics of patient-centred communication and empathy (through presentations, scientific literature), (2) practicing with actors, and (3) reflecting on residents' video recorded consultations (by themselves and communication experts). A pilot study with a pre-post design was conducted to evaluate the training from patient and observer perspectives. Semi-structured interviews were used to get insight into residents' perspective. Nine residents from different specialities followed the training and enrolled in the pilot study. During two random days consultations between residents and patients were video recorded. Patients were asked to fill in two questionnaires, indicating their perspective on residents' empathy and communication skills before as well as after the consultation. All video recorded consultations were coded to rate residents' communication skills, empathy, computer use and agenda-setting. Statistical analysis were performed using multilevel analysis.
A total of 137 eligible patients took part in the pilot study. Trained residents showed significant improvement in patient-rated empathy scores. According to observers, residents' computer use improved significantly after the training. The communication skills of trained residents did not improve significantly. Agenda setting by residents showed a downward trend. Almost all residents were satisfied with the training, especially with the video-feedback.
A brief training significantly increased residents' empathy scores according to patients and significantly decreased residents' computer use according to observers. These findings indicate that the quality of patient-centred care can be improved by integrating patient-centred communication into residency programs, at an academic medical health centre. The ultimate goal is to structurally embed the training in residents' education program.
Many studies have compared real-world clinical outcomes of immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) with reported outcomes data from pivotal trials. However, any ...differences observed could be only limitedly explored further for causation because of the unavailability of individual patient data (IPD) from trial participants. The present study aims to explore the additional benefit of comparison with IPD.
This study compares progression free survival (PFS) and overall survival (OS) of metastatic NSCLC patients treated with second line nivolumab in real-world clinical practice (n = 141) with IPD from participants in the Checkmate-057 clinical trial (n = 292). Univariate and multivariate Cox proportional hazards models were used to construct HRs for real-world practice versus clinical trial.
Real-world patients were older (64 vs. 61 years), had more often ECOG PS ≥ 2 (5 vs. 0%) and were less often treated with subsequent anti-cancer treatment (28.4 vs. 42.5%) compared to trial patients. The median PFS in real-world patients was longer (3.84 (95%CI: 3.19-5.49) vs 2.30 (2.20-3.50) months) and the OS shorter than in trial participants (8.25 (6.93-13.2) vs. 12.2 (9.90-15.1) months). Adjustment with available patient characteristics, led to a shift in the hazard ratio (HR) for OS, but not for PFS (HRs from 1.13 (0.88-1.44) to 1.07 (0.83-1.38), and from 0.82 (0.66-1.03) to 0.79 (0.63-1.00), respectively).
This study is an example how IPD from both real-world and trial patients can be applied to search for factors that could explain an efficacy-effectiveness gap. Making IPD from clinical trials available to the international research community allows this.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to provide insights into the real-world use of palbociclib, dose reductions, and drug effectiveness in (older) patients with advanced breast cancer (BC).
Patients with advanced BC ...treated with palbociclib from 2017 to 2020 were included. The Kaplan-Meier method was used to calculate time to next treatment (TTNT) and overall survival (OS) for patients with or without dose reductions. These clinical outcomes were also compared in subgroup analyses for older patients (≥70 years) and younger patients (<70 years) and for patients discontinuing palbociclib early (<4 administrations).
A total of 598 patients with advanced BC were included, with a median age of 64 years. Palbociclib dose reductions occurred in 33% of all patients. Early discontinuation of palbociclib without dose reductions occurred in 23% of the patients. Patients who required a palbociclib dose reduction were older (median age 67 years vs. 63 years). Patients with dose reductions had a significantly higher TTNT of 16.9 vs. 11.4 months (p < 0.001) and median OS of 29.7 vs. 21.9 months (p = 0.003) compared to patients without dose reductions. The TTNT in older patients was significantly longer (16.9 vs. 11.6 months, p = 0.013) than younger patients, but OS was similar (20.7 vs. 26.7 months, p = 0.051).
Palbociclib dose reductions occurred in real-world practice similarly to the PALOMA-3 trial. Patients with dose reductions had no poorer outcomes compared to patients not requiring a dose reduction. Older patients treated with palbociclib had more frequent dose reductions, but this did not appear to affect OS.
•Palbociclib dose reductions occurred in 33% of the real-world patients.•Dose reductions did not lead to poorer overall survival.•Older patients had more dose reductions, but this did not affect overall survival.
Exercise is one of the external factors associated with impairment of intestinal integrity, possibly leading to increased permeability and altered absorption. Here, we aimed to examine to what extent ...endurance exercise in the glycogen‐depleted state can affect intestinal permeability toward small molecules and protein‐derived peptides in relation to markers of intestinal function. Eleven well‐trained male volunteers (27 ± 4 years) ingested 40 g of casein protein and a lactulose/rhamnose (L/R) solution after an overnight fast in resting conditions (control) and after completing a dual – glycogen depletion and endurance – exercise protocol (first protocol execution). The entire procedure was repeated 1 week later (second protocol execution). Intestinal permeability was measured as L/R ratio in 5 h urine and 1 h plasma. Five‐hour urine excretion of betacasomorphin‐7 (BCM7), postprandial plasma amino acid levels, plasma fatty acid binding protein 2 (FABP‐2), serum pre‐haptoglobin 2 (preHP2), plasma glucagon‐like peptide 2 (GLP2), serum calprotectin, and dipeptidylpeptidase‐4 (DPP4) activity were studied as markers for excretion, intestinal functioning and recovery, inflammation, and BCM7 breakdown activity, respectively. BCM7 levels in urine were increased following the dual exercise protocol, in the first as well as the second protocol execution, whereas 1 h‐plasma L/R ratio was increased only following the first exercise protocol execution. FABP2, preHP2, and GLP2 were not changed after exercise, whereas calprotectin increased. Plasma citrulline levels following casein ingestion (iAUC) did not increase after exercise, as opposed to resting conditions. Endurance exercise in the glycogen depleted state resulted in a clear increase of BCM7 accumulation in urine, independent of DPP4 activity and intestinal permeability. Therefore, strenuous exercise could have an effect on the amount of food‐derived bioactive peptides crossing the epithelial barrier. The health consequence of increased passage needs more in depth studies.
This study shows that there is adaptation seen with repeated exercise for intestinal permeability with the classical sugar test. This adaptation is not seen for the increased amount of the betacasomorphin‐7 peptide excreted in urine following strenuous exercise compared to rest.
studies suggest that intestinal barrier integrity is dependent on mitochondrial ATP production. Here, we aim to provide mechanistic support, using an
model mimicking the oxidative
situation.
Human ...Caco-2 cells were cultured for 10 days in culture flasks or for 14 days on transwell inserts in either glucose-containing or galactose-containing medium. Mitochondria were visualized and cellular respiration and levels of oxidative phosphorylation (OXPHOS) proteins were determined. Mitochondrial ATP depletion was induced using CCCP, rotenone, or piericidin A (PA). Monolayer permeability was assessed using transepithelial electrical resistance (TEER) and fluorescein flux. Gene expression and cellular distribution of tight junction proteins were analyzed.
Caco-2 cells cultured in galactose-containing, but not in glucose-containing, medium showed increased mitochondrial connectivity, oxygen consumption rates and levels of OXPHOS proteins. Inhibition of mitochondrial ATP production using CCCP, rotenone or PA resulted in a dose-dependent increase in Caco-2 monolayer permeability. In-depth studies with PA showed a six fold decrease in cellular ATP and revealed increased gene expression of tight junction proteins (
) 1 and 2, occludin, and claudin 1, but decreased gene expression of claudin 2 and 7. Of these, claudin 7 was clearly redistributed from the cellular membrane into the cytoplasm, while the others were not (TJP1, occludin) or slightly (claudin 2, actin) affected.
studies suggest that intestinal barrier integrity is dependent on mitochondrial ATP production. Here, we aim to provide mechanistic support, using an
model mimicking the oxidative
situation.
Well-functioning mitochondria are essential for maintaining cellular energy status and monolayer integrity of galactose grown Caco-2 cells. Energy depletion-induced Caco-2 monolayer permeability may be facilitated by changes in the distribution of claudin 7.
•The establishment of the DLCA-L led to insights and improvements in hospital care.•The DLCA-L data visualize real-world use of systemic therapies.•Real-world use of immunotherapy differs from trial ...setting.
This study describes the initiation of the Dutch Lung Cancer Audit for Lung Oncology (DLCA-L) and reports the first results of three years of clinical auditing.
The initiation, dataset, and data quality of the DLCA-L are described. For the analyses, all patients registered from 2017 to 2019 were included. Descriptive statistics were used to assess the first outcomes of the DLCA-L, including results from quality indicators, patient- and tumor characteristics, and the real-world use of immunotherapy.
The DLCA-L was initiated after the surgery and radiotherapy audit for lung cancer. In total, 33.788 NSCLC patients and 4.293 SCLC patients were registered in the DLCA-L from 2017 to 2019. Seventy-three (97 %) Dutch hospitals participated in the DLCA-L in 2019. The registry became nation-wide in 2020. The data quality improved over the years, with complete cases in 90 % of the NSCLC patients. In total, 15 quality indicators were established based on DLCA-L data to improve processes and clinical outcomes. An example of these quality indicators was brain imaging at diagnosis of stage III NSCLC patients, which increased from 80 % in 2017 to 90 % in 2019 and hospital variation was reduced. The DLCA-L provided data on immunotherapy use in stage IV NSCLC (n = 4.415) patients. These patients had a median age of 67 years and 11 % of the patients had an ECOG PS ≥ 2. The number of patients treated with immunotherapy in different hospitals varied between 2 patients to 163 patients per hospital.
The DLCA-L has become a valuable and complete data source with national coverage in 2020. A high number of registered patients and limited missing data resulted in better insights into hospital processes and outcomes of lung cancer care. Quality indicators were, with success, used to establish improvements and minimize hospital variation. The DLCA-L also provides hospitals real-world information on the use of (systemic) therapies.
The embryonic stem cell test (EST) has been designed to predict developmental toxicity based upon compound-induced inhibition of embryonic stem cell (ESC) differentiation. The end point scoring, the ...test duration, and the definition of the predictivity and the applicability domain require improvements to facilitate implementation of the EST into regulatory testing strategies. The use of transcriptomics to study compound-induced differentiation modulation may improve the EST in each of these aspects. ESC differentiation was induced, and cell samples were collected after 0, 24, and 48 h of differentiation. Additionally, samples were collected that were 24 h exposed to one of five developmentally toxic compounds or a nondevelopmentally toxic compound. All samples were hybridized to Affymetrix GeneChips, and analyses revealed that 26 genes were significantly regulated both during ESC differentiation and by exposure to each of the developmentally toxic compounds tested. Using principal component analysis, we defined a “differentiation track” on the basis of this gene list, which represents ESC differentiation. We showed that significant deviation from the differentiation track was in line with the developmental toxic properties of the compounds. The significance of deviation was analyzed using the leave-one-out cross-validation, which showed a favorable prediction of toxicity in the system. Our findings show that gene expression signatures can be used to identify developmental toxicant–induced differentiation modulation. In addition, studying compound-induced effects at an early stage of differentiation combined with transcriptomics leads to increased objectivity in determining differentiation inhibition and to a reduction of the test duration. Furthermore, this approach may improve the predictivity and applicability domain of the EST.
Scope
Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic ...health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR.
Design and methods
Nine‐week‐old male C57BL/6JRcc mice received a semi‐purified mildly obesogenic (40 en% fat) diet containing 0.14% L‐tryptophan and either 5, 15, 30, 180, or 900 mg NR per kg diet for 15 weeks. Body composition and metabolic parameters were analyzed. Metabolic flexibility was measured using indirect calorimetry. Gene expression in epididymal white adipose tissue (eWAT) was measured using qRT‐PCR .
Results
The maximum delta respiratory exchange ratio when switching from CHO to FAO (maxΔRERCHO1→FAO) and when switching from FAO to CHO (maxΔRERFAO→CHO2) were largest in 30 mg NR per kg diet (30NR). In eWAT, the gene expression of Pparγ, a master regulator of adipogenesis, and of Sod2 and Prdx3, two antioxidant genes, were significantly upregulated in 30NR compared to 5NR.
Conclusion
30NR is most beneficial for metabolic health, in terms of metabolic flexibility and eWAT gene expression, of mice on an obesogenic diet.
To determine the optimal concentration of vitamin B3 in the diet, a wide range of nicotinamide riboside (NR) was given to C57Bl/6JRcc mice. A defined human relevant diet with low tryptophan levels was used. Metabolic flexibility, serum parameters and white adipose tissue were examined. Surprisingly the effects were small. 30 mg NR/kg diet was most beneficial for metabolic health.
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