Аксіологічні виміри душпастирства у творах Іоана Золотоустого

Стаття Світлани Білоус "Аксіологічні виміри душпастирства у творах Іоана Золотоустого" присвячена пошуку джерел духовної опіки над людиною, витоки яких автор бачить у християнському середньовіччі. Життя і творча спадщина Іоана Золотоустого – яскравий приклад пояснення сутності й визначення ціннісної природи душпастирювання крізь призму поняття священства.Статья Светланы Билоус "Аксиологические измерения душпастирства в произведениях Іоана Золотоустого" посвящена поиску источников духовной опеки над человеком, истоки которіх автор видит в христианском средневековье. Жизнь и творческое наследство Иоанна Золотоустого – яркий пример объяснения сущности и определение ценностной природы душпастирства сквозь призму понятия священства.The article by Svitlana Bilous "Axiological dimensions of priesthood in the Ioan Zolotoustyi’s works" is dedicated to finding sources of spiritual care over a human, the origin of which the author sees in the Christian Middle Ages. The life and literary heredity of Ioan Zolotoustyi is a brilliant pattern of explaining the essence and definition of valuable ​​nature of pastoral care through the prism of the concept of the priesthood

AR splice variants in circulating tumor cells of patients with castration-resistant prostate cancer: relation with outcome to cabazitaxel

The androgen receptor splice variant (AR-V) 7 in circulating tumor cells (CTCs) is a predictor for resistance to anti-AR-targeted treatment, but not to taxane-based chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). In this study, we investigated whether the presence of two constitutively active variants (AR-V3, AR-V7) and two other conditionally activated variants (AR-V1, AR-V9) vs full-length androgen receptor (AR-FL) measured in CTCs from patients with mCRPC were associated with outcome to therapy with the taxane cabazitaxel. Blood was collected at baseline and after two cycles of cabazitaxel from 118 mCRPC patients starting cabazitaxel in a prospective phase II trial. CellSearch-enriched CTCs were enumerated and in parallel characterized for the presence of the AR-Vs by reverse transcription quantitative polymerase chain reaction. Correlations with CTC and prostate-specific antigen response to cabazitaxel as well as associations with overall survival (OS) were investigated. All AR-Vs were frequently pre

Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients

Background: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial. Patients and methods: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients. Results: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: −3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (−7.4 and −8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570. Conclusion: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impac

Circulating tumor cell enumeration and characterization in metastatic castration-resistant prostate cancer patients treated with cabazitaxel

(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles of circulating tumor cells (CTCs). (2) Methods: From 120 mCRPC patients, CellSearch enriched CTCs were obtained at baseline and after 6 weeks of cabazitaxel therapy. Furthermore, 91 genes associated with prostate cancer were measured in mRNA of these CTCs. (3) Results: In 114 mCRPC patients with an evaluable CTC count, the CTC count was independently associated with poor progression-free survival (PFS) and overall survival (OS) in multivariable analysis with other commonly used variables associated with outcome in mCRPC (age, prostate specific antigen (PSA), alkaline phosphatase, lactate dehydrogenase (LDH), albumin, hemoglobin), together with alkaline phosphatase and hemoglobin. A five-gene expression profile was generated to predict for outcome to cabazitaxel therapy. However, even though this signature was associated with OS in univariate analysis, this was not the case in the multivariate analysis for OS nor for PFS. (4) Conclusion: The established five-gene expression profile in CTCs was not independently associated with PFS nor OS. However, along with alkaline phosphatase and hemoglobin, CTC-count is independently associated with PFS and OS in mCRPC patients who are treated with cabazitaxel

Prevalence and treatment of anemia and secondary iron overload in patients with a myelodysplastic syndrome: Real-world data from a multicenter cohort study

Background: anemia is the most common finding in patients with a myelodysplastic syndrome (MDS). Repetitive red blood cell (RBC) transfusions and disease-related low hepcidin levels induce secondary iron overload. Real-world data on the prevalence and treatment strategies of anemia and secondary iron overload in MDS patients, is limited. Methods: three years of data on MDS diagnosis, anemia and ferritin management was collected in 230 MDS patients from seven non-academic hospitals in the Netherlands. Descriptive statistics and linear mixed models were used to analyze the data. Results: transfusion dependent (TD) patients (n = 49) needed 1–3 RBC transfusions per month. Serum hemoglobin remained stable in both TD and transfusion-independent (TI) patients over 3 years. In the TD patients, serum ferritin increased 63 pmol/L/month. Overall, 19 (39%) were diagnosed with secondary hemochromatosis, of which 13 (68%) received chelation therapy with a heterogeneous response. Conclusions: mean hemoglobin remains stable over time in both TD and TI MDS patients. Approximately 40% of TD patients develop secondary hemochromatosis. Treatment and monitoring of secondary hemochromatosis as well as the response on chelation therapy vary substantially

Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial

In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication. We did this double-blind, randomised, placebo-controlled phase 2 trial at four centres in the Netherlands. Patients aged 18 years or older with advanced pancreatic cancer were randomly assigned (1:1), via a permutated computer-generated block allocation scheme (block size of six) to receive intravenous gemcitabine (1000 mg/m(2)) on days 1, 8, and 15 every 4 weeks and oral erlotinib (100mg) once daily in combination with either oral metformin or placebo twice daily. Metformin dose was escalated from 500 mg (in the first week) to 1000 mg twice daily in the second week. Randomisation was stratified by hospital, diabetes status, and tumour stage. The primary endpoint was overall survival at 6 months in the intention-to-treat population. This trial is complete and is registered with ClinicalTrials.gov, number NCT01210911. Between May 31, 2010, and Jan 3, 2014, we randomly assigned 121 patients to receive gemcitabine and erlotinib with either placebo (n=61) or metformin (n=60). Overall survival at 6 months was 63·9% (95% CI 51·9-75·9) in the placebo group and 56·7% (44·1-69·2) in the metformin group (p=0·41). There was no difference in overall survival between groups (median 7·6 months [95% CI 6·1-9·1] vs 6·8 months [95% CI 5·1-8·5] in the metformin group; hazard ratio [HR] 1·056 [95% CI 0·72-1·55]; log-rank p=0·78). The most frequent grade 3-4 toxic effects were neutropenia (15 [25%] patients in placebo group vs 15 [25%] in metformin group), skin rash (six [10%] vs four [7%]), diarrhoea (three [5%] vs six [10%]), and fatigue (two [3%] vs six [10%]). Addition of a conventional anti-diabetic dose of metformin does not improve outcome in patients with advanced pancreatic cancer treated with gemcitabine and erlotinib. Future research should include studies of more potent biguanides, and should focus on patients with hyperinsulinaemia and patients with tumours showing markers of sensitivity to energetic stress, such as loss of function of AMP kinase, a key regulator of cellular energy homoeostasis. Academic Medical Centre, Amsterdam, and The Terry Fox Foundation, Vancouver, Canad

Adherence and patients’ experiences with the use of capecitabine in daily practice

Background: Capecitabine is a widely prescribed oral anticancer agent. We studied medication adherence and explored its use in daily practice from a patients’ perspective. Methods: Patients (n=92) starting capecitabine were followed up to five 3-week cycles. Adherence was assessed using a pill count, pharmacy data and dosing information from the patients’ medical file. Self-reported adherence was measured using the Medication Adherence Report Scale (MARS). At baseline and during week 2 of cycles 1, 3 and 5, patients filled out questionnaires about quality of life, symptoms, attitude towards medicines and disease and use in daily practice. Simultaneously, blood samples were taken to determine the area under the curve (AUC) of 5’-deoxy-5-fluorouridine (5’-DFUR), 5-fluorouracil (5-FU) and α-fluoro-β-alanine (FBAL) by a population pharmacokinetic model. Associations between AUCs and patient-reported symptoms were tested for cycles 3 and 5.Results: Most patients (84/92; 91%) had an adherence rate of ≥95% and ≤105%. The percentage of patients reporting any non-adherence behaviour measured with MARS increased from 16% at cycle 1 to 29% at cycle 5. Symptoms were reported frequently and the dosing regimen was adjusted by the physician at least once in 62% of patients. In multivariate analysis the probability of an adjustment increased with the number of co-medication (OR 1.19, 95%CI:1.03-1.39) and a stronger emotional response to the disease (OR 1.32, 95%CI:1.10-1.59)..The AUC of 5’-DFUR was associated with weight loss (OR 1.10, 95%CI:1.01-1.19), AUC of FBAL with hand-foot syndrome (OR 0.90, 95%CI:0.83-0.99), rhinorrhea (OR 1.21, 95%CI:1.03-1.42 weight loss (OR 1.09, 95%CI:1.00-1.20) and depression (OR 0.90, 95%CI:0.82-0.99). Side effects were reported by one third of patients as the reason to discontinue treatment.Conclusion: Adherence to capecitabine was generally high. Nevertheless, adherence measured with MARS decreased over time Adherence management to support implementation of correct capecitabine use is specifically relevant in longer term treatment. In addition, it appears that adverse event management is important to support persistence. With the extending armamentarium of oral targeted anticancer agents and prolonged treatment duration, we expect the issue of medication adherence of increasing importance in oncology

Accuracy of the Delirium Observational Screening Scale (DOS) as a screening tool for delirium in patients with advanced cancer

Background: The Delirium Observation Screening Scale (DOS) was developed to facilitate early recognition of delirium by nurses during routine clinical care. It has shown good validity in a variety of patient populations, but has not yet been validated in hospitalized patients with advanced cancer, although the DOS is commonly used in this setting in daily practice. The aim of this study was to evaluate the accuracy of the DOS in hospitalized patients with advanced cancer using the revised version of the Delirium Rating Scale (DRS-R - 98 ) as the gold standard. Methods: Patients with advanced cancer admitted to the medical oncology ward were screened for delirium with the DOS and DRS-R-98. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the DOS were calculated, using a DOS score ≥ 3 as a cut-off for delirium. Results: Ninety-five DOS negative and 98 DOS positive patients were identified. Sensitivity of the DOS, was > 99.9% (95%-CI, 95.8-100.0%), specificity was 99.5% (95%-CI 95.5-99.96%), PPV was 94.6% (95% CI 88.0-97.7), and NPV was > 99.9% (95% CI 96.1-100.0). Conclusions: The DOS is an accurate screening tool for delirium in patients with advanced cancer. Since it has the benefit of being easily implicated in daily practice, we recommend to educate caregivers to screen patients with advanced cancer by DOS analysis. By early recognition and adequate treatment of this distressing delirium syndrome the quality of life of patients with advanced cancer can be improved. Trial registration: ClinicalTrials.gov Identifier NCT01539733 (Feb 27, 2012 - retrospectively registered), Netherlands Trial Register NTR2559 (Oct 7, 2010)