Men?s preferences for treatment of early stage prostate cancer: Results from a discrete choice experiment, CHERE Working Paper 2006/14

Prostate cancer is the most common cancer in men in Australia; each year over 10,000 Australians are diagnosed with this disease. There are a number of treatment options for early stage prostate cancer (ESPC); radical prostatectomy, external beam radiotherapy, brachytherapy, hormonal therapy and combined therapy. Treatment can cause serious side-effects, including severe sexual and urinary dysfunction, bowel symptoms and fatigue. Furthermore, there is no evidence as yet to demonstrate that any of these treatments confers a survival gain over active surveillance (watchful waiting). While patient preferences should be important determinants in the type of treatment offered, little is known about patients? views of the relative tolerability of side effects and of the survival gains needed to justify these. To investigate this, a discrete choice experiment (DCE) was conducted in a sample of 357 men who had been treated for ESPC and 65 age-matched controls. The sample was stratified by treatment, with approximately equal numbers in each treatment group. The DCE included nine attributes: seven side-effects and two survival attributes (duration and uncertainty). An orthogonal fractional set of 108 scenarios from the full factorial was used to generate three versions of the questionnaire, with 18 scenarios per respondent. Multinomial logit (MNL) and mixed logit (MXL) models were estimated. A random intercept MXL model provided a significantly better fit to the data than the simple MNL model, and adding random coefficients for all attributes dramatically improved model fit. Each side-effect had a statistically significant mean effect on choice, as did survival duration. Most attributes had significant variance parameters, suggesting considerable heterogeneity among respondents in their preferences. To model this heterogeneity, we included men?s health-related quality of life scores following treatment as covariates to see whether their preferences were influenced by their previous treatment experience. This study demonstrate how DCEs can be used to quantify the trade-offs patients make between side-effects and survival gains. The results provide useful insights for clinicians who manage patients with ESPC, highlighting the importance of patient preferences in treatment decisions.Prostate cancer, discrete choice experiment, preferences, quality of life

Serum levels of oxylipins in achilles tendinopathy: An exploratory study

Background: Linoleic acid-derived oxidation products are found in experimental pain models. However, little is known about the levels of such oxylipins in human pain. In consequence, in the present study, we have undertaken a lipidomic profiling of oxylipins in blood serum from patients with Achilles tendinopathy and controls. Methodology/Principal findings: A total of 34 oxylipins were analysed in the serum samples. At a significance level of P<0.00147 (<0.05/34), two linoleic acid-derived oxylipins, 13-hydroxy-10E,12Z-octadecadienoic (13-HODE) and 12(13)-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) were present at significantly higher levels in the Achilles tendinopathy samples. This difference remained significant when the dataset was controlled for age, gender and body-mass index. In contrast, 0/21 of the arachidonic acid- and 0/4 of the dihomo-γ-linolenic acid, eicosapentaenoic acid or docosahenaenoic acid-derived oxylipins were higher in the patient samples at this level of significance. The area under the Receiver-Operator Characteristic (ROC) curve for 12,13-DiHOME was 0.91 (P<0.0001). Levels of four N-acylethanolamines were also analysed and found not to be significantly different between the controls and the patients at the level of P<0.0125 (<0.05/4). Conclusions/Significance: It is concluded from this exploratory study that abnormal levels of linoleic acid-derived oxylipins are seen in blood serum from patients with Achilles tendinopathy. Given the ability of two of these, 9- and 13-HODE to activate transient receptor potential vanilloid 1, it is possible that these changes may contribute to the symptoms seen in Achilles tendinopathy

Function, Adjustment, Quality of Life and Symptoms (FAQS) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Survivors: A Study Protocol

<p>Abstract</p> <p>Background</p> <p>The population of survivors following allogeneic HSCT continues to increase, and yet their experiences of recovery and long-term survivorship have not been fully characterized. This paper presents a study protocol examining over time the functional status, psychosocial adjustment, health-related quality of life, and symptom experience of survivors who have undergone allogeneic transplantation. The aims of the study are to: 1) explore the patterns of change in these health outcomes during the survivorship phase; 2) characterize subgroups of survivors experiencing adverse outcomes; and 3) examine relationships among outcomes and demographic and clinical factors (such as age, graft-versus-host disease (GVHD), and disease relapse).</p> <p>Methods</p> <p>In this longitudinal observational study, adults who survive a minimum of 3 years from date of allogeneic transplantation complete a series of questionnaires annually. Demographic and clinical data are collected along with a series of patient-reported outcome measures, specifically: 1) Medical Outcomes Study SF- 36; 2) Functional Assessment of Chronic Illness Therapy (FACIT) - General, 3) FACIT-Fatigue; 4) FACIT- Spiritual; 5) Psychosocial Adjustment to Illness Scale; 6) Rotterdam Symptom Checklist-Revised; and 7) Pittsburgh Sleep Quality Index.</p> <p>Conclusions</p> <p>This study will provide multidimensional patient-reported outcomes data to expand the understanding of the survivorship experience across the trajectory of allogeneic transplantation recovery. There are a number of inherent challenges in recruiting and retaining a diverse and representative sample of long-term transplant survivors. Study results will contribute to an understanding of outcomes experienced by transplant survivors, including those with chronic GVHD, malignant disease relapse, and other late effects following allogeneic transplantation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00128960">NCT00128960</a></p

Noninvasive evaluation of hand circulation before radial artery harvest for coronary artery bypass grafting

AbstractObjective: Radial artery harvesting for coronary artery bypass may lead to digit ischemia if collateral hand circulation is inadequate. The modified Allen's test is the most common preoperative screening test used. Unfortunately, this test has high false-positive and false-negative rates. The purpose of this study was to compare the results of a modified Allen's test with digit pressure change during radial artery compression for assessing collateral circulation before radial artery harvest. Methods: One hundred twenty-nine consecutive patients were studied before coronary artery bypass operations. A modified Allen's test was performed with Doppler ultrasound to assess blood flow in the superficial palmar arch before and during radial artery compression. A decreased audible Doppler signal after radial artery compression was considered a positive modified Allen's test. First and second digit pressures were measured before and during radial artery compression. A decrease in digit pressure of 40 mm Hg or more (digit ΔP) with radial artery compression was considered positive. Results: Seven of 14 dominant extremities (50%) and 8 of the 16 nondominant extremities (50%) with a positive modified Allen's test had a digit ΔP of less than 40 mm Hg (false positive). Sixteen of 115 dominant extremities (14%) and 5 of 112 nondominant extremities (4%) with a negative Allen's test had a digit ΔP of 40 mm Hg or more with radial artery compression (false negative). Conclusion: Use of the modified Allen's test for screening before radial artery harvest may unnecessarily exclude some patients from use of this conduit and may also place a number of patients at risk for digit ischemia from such harvest. Direct digit pressure measurement is a simple, objective method that may more precisely select patients for radial artery harvest. Additional studies are needed to define objective digital pressure criteria that will accurately predict patients at risk for hand ischemia after radial harvest. (J Thorac Cardiovasc Surg 1999;117:261-6

Мотивация и ее методы социально-психологического стимулирования

Материалы XVIII Междунар. науч.-техн. конф. студентов, аспирантов и молодых ученых, Гомель, 26–27 апр. 2018 г

Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: Laboratory Detection and Impact on Mortality

Background: Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. Methods: A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014. Reference colistin resistance determination as performed by broth macrodilution was compared to results from clinical microbiology laboratories (Etest) and to polymyxin resistance testing. Each patient was included once, at the time of their first colistin-tested CRKp positive culture. Time to 30-day in-hospital all-cause mortality was evaluated by Kaplan-Meier curves and Cox proportional hazard modeling. Results: In 246 patients with CRKp, 13% possessed ColR CRKp. ColR was underestimated by Etest (very major error rate = 35%, major error rate = 0.4%). A variety of rep-PCR strain types were encountered in both the ColS and the ColR groups. Carbapenem resistance was mediated primarily by blaKPC-2 (46%) and blaKPC-3 (50%). ColR was associated with increased hazard for in-hospital mortality (aHR 3.48; 95% confidence interval, 1.73-6.57; P < .001). The plasmid-associated ColR genes, mcr-1 and mcr-2 were not detected in any of the ColR CRKp. Conclusions: In this cohort, 13% of patients with CRKp presented with ColR CRKp. The apparent polyclonal nature of the isolates suggests de novo emergence of ColR in this cohort as the primary factor driving ColR. Importantly, mortality was increased in patients with ColR isolates

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease