Reasons for continuous sedation until death in cancer patients: a qualitative interview study.

End-of-life sedation, though increasingly prevalent and widespread, remains a highly debated medical practice in the context of palliative medicine. This qualitative study aims to look more specifically at how health care workers justify their use of continuous sedation until death and which factors they report as playing a part in the decision-making process. In-depth interviews were held with 28 physicians and 22 nurses of 27 cancer patients in Belgium who had received continuous sedation until death in hospitals, palliative care units or at home. Our findings indicate that medical decision-making for continuous sedation is not only based on clinical indications but also related to morally complex issues such as the social context and the personal characteristics and preferences of individual patient and their relatives. The complex role of non-clinical factors in palliative sedation decision-making needs to be further studied to assess which medically or ethically relevant arguments are underlying daily clinical practice. Finally, our findings suggest that in some cases continuous sedation was resorted to as an alternative option at the end of life when euthanasia, a legally regulated option in Belgium, was no longer practically possible.

[Clinical and Functional Importance of Selected CASP8 and CASP9 Polymorphisms in Breast Carcinoma]. / Klinický a funkcní význam vybraných polymorfizmu CASP8 a CASP9 u karcinomu prsu.

BACKGROUND: Caspase-8 and caspase-9 (encoded by CASP8 and CASP9) are executive caspases of programmed cell death (apoptosis). Dysregulation of apoptosis plays an important role in cancer development, progression, and resistance to anticancer therapy. The goal of this work was to evaluate potential associations between polymorphisms in CASP8 and CASP9, previously linked to breast cancer risk, and the transcript levels of these genes (including their alternative anti-apoptotic variants) in tumor tissues and the clinical characteristics of the patients. MATERIAL AND METHODS: Sanger sequencing, high resolution melting (HRM) analysis, and allelic discrimination were used to identify polymorphisms in DNA samples isolated from tumor tissues and peripheral blood lymphocytes of 60 breast carcinoma patients. Total transcript levels of CASP8 and CASP9, and levels of alternative splicing variants CASP8L and CASP9B, were quantified by real-time PCR in tumor tissues. Clinically interesting associations were validated in DNA from lymphocytes of 615 breast carcinoma patients. RESULTS: A haplotype in CASP9 composed of three polymorphisms rs4645978-rs2020903-rs4646034 was significantly associated with CASP9 expression in tumors, with the expression of the progesterone receptor and ERBB2, and with the TNBC subtype of breast carcinoma in the validation study. The associations between the rs3834129 polymorphism in CASP8 and stage of disease, rs6435074 with grade, expression of estrogen receptor and ERBB2, and rs6723097 with ERBB2 expression have not yet been validated. However, rs6723097 was associated with disease-free survival in patients treated with hormonal therapy. CONCLUSION: This study reveals a previously unknown and presumably functional (in silico) association between a haplotype in CASP9 and molecular and clinical phenotypes of breast carcinoma. The potential clinical utility of this association for prognostication of breast carcinoma should be evaluated by independent studies.Key words: breast carcinoma - caspases - polymorphisms - functional - clinical - importanceThis work was supported by grant of the CU Grant Agency No. 1444313, and grant of the Internal Grant Agency of the Czech Ministry of Health No. 15-25618A.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 3. 3. 2016Accepted: 26. 10. 2016.

[Breast cancer cell populations and its changes relation to therapy]. / Populace bunek karcinomu prsu a její zmeny v závislosti na protinádorové lécbe.

This review summarizes the data from published studies that dealt with observation of various bioparameters changes in cancer population dependant on used therapy. Critically evaluating these studies and looking for relations among separate results we are trying to estimate prognostic value of these parameters (likelihood of recurrence, overall survival, ...) and also their value for prediction of tumor response to cytostatic, hormonal or other treatment. The aim is selection of such tumor population characteristics the testing of them would enable better patient stratification in postoperative adjuvant systemic therapy.

Whole exome sequencing analysis of ABCC8 and ABCD2 genes associating with clinical course of breast carcinoma.

The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance.

[Hormone therapy and urogynecology]. / Hormonální lécba a urogynekologie.

The female genital and urinary systems exists in close anatomical and functional proximity, disorders of one resulting in dysfunction of the other. The investigation and management of lower urinary tract disorders must take this important relationship into consideration, as neither can be viewed in isolation. The value of estrogen replacement therapy as a treatment of urinary incontinence is controversial and until today there is a little substantial evidence to conclude that estrogen therapy alone is of value in the treatment of this symptom. This conflicting evidence concerning the therapeutic benefit of estrogen therapy in stress urinary incontinence seems to be outweighed with other advantages of estrogen replacement therapy. Clear evidence exists to suggest that recurrent urinary tract infections can be prevented or even treated by the use of estrogen therapy. Systemic estrogen replacement appears to relieve the symptoms of urgency, urge incontinence, frequency, nycturia and dysuria, and low-dose topical estrogen is effective in the management of atrophic vaginitis. Even with postulating the HRT to be of enormous therapeutic value to postmenopausal women in urogynecology it may stay only a mean of support of other causal methods of treatment of dysfunction of lower urinary tract.

[Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo]. / Lécba cyklické mastodynie pomocí roztoku s extraktem z Vitex agnus castus: výsledky dvojite slepé studie ve srovnání s placebem.

The aim of study presented here was to gather the data about the tolerability and efficacy of Vitex agnus castus (VACS) extract. The study was designed as double-blind, placebo controlled in two parallel groups (each 50 patients). Treatment phase lasted 3 consequent menstrual cycles (2 x 30 drops/day = 1.8 ml of VASC) or placebo. Mastalgia during at least 5 days of the cycle before the treatment was the strict inclusion condition. For assessment of the efficacy visual analogue scale was used. Altogether 97 patients were included into the statistical analysis (VACS: n = 48, placebo: n = 49). Intensity of breast pain diminished quicker with VACS group. The tolerability was satisfactory. We found VACS to be useful in the treatment of cyclical breast pain in women.

[Tolerance and effectiveness of propiverine hydrochloride in 752 patients with symptoms of detrusor hyperactivity and increased sensitivity and irritability of the urinary bladder: results of a study monitoring drug utilization]. / Snásenlivost a úcinnost propiverinhydrochloridu u 752 pacientu s príznaky hyperaktivity detruzoru, zvýsené senzitivity a drázdivosti mocového mechýre: výsledky studie sledování pouzití léku.

In a post-marketing surveillance study of 752 patients suffering from urgent incontinence, mixed urgent-stress incontinence, reflex incontinence, urgency and enuresis were treated with propiverine hydrochloride. Clinical efficacy of propiverine hydrochloride was verified by the improvement of symptoms related to detrusor hyperactivity, hypersensitivity and hyperreflexia during a 12-week surveillance period: daytime and overnight urinary incontinence, as well as the frequency, nocturia, urgency in day time and at night decreased. These results are well demonstrated by decreased pad use and statistically significant decrease of Gaudenz urgency score during treatment, confirming the efficacy of propiverine hydrochloride already proved in clinical trials. The safety profile of propiverine hydrochloride displayed characteristic anticholinergic symptoms (dry mouth, accommodation disorders, constipation, tiredness, dizziness) with decreasing incidence during the 12-week treatment period. The residual urine volume decreased also. Serious adverse events were observed rarely and could be explained by the lack of consideration of contraindications, warnings and interactions with other drugs. The positive risk-benefit relationship of propiverine hydrochloride in the treatment of detrusor hyperactivity, hypersensitivity and hyperreflexia was reconfirmed in this post-marketing drug surveillance study.