| 1. |
- Johnson, Heather, et al.
(författare)
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Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up
- 2020
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. Methods: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRTPCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. Results: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963–0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929–0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956–0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980–0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947–0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. Conclusions: The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.
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| 2. |
- Franzén, Karin M, 1958-, et al.
(författare)
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Surgery for urinary incontinence in women 65 years and older : a systematic review
- 2015
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Ingår i: International Urogynecology Journal. - : Springer. - 0937-3462 .- 1433-3023. ; 26:8, s. 1095-1102
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Forskningsöversikt (refereegranskat)abstract
- Introduction and hypothesis: Urinary incontinence (UI) is common among the elderly, but the literature is sparse on the surgical treatment of UI among the elderly. This systematic review aims to assess the effectiveness of surgical interventions as treatment for urinary incontinence in the elderly population ≥65 years of age.Methods: Randomized controlled trials (RCT) and prospective nonrandomized studies (NRS) were included. The databases PubMed (NLM), EMBASE (Elsevier), Cochrane Library (Wiley), and Cinahl (EBSCO) were searched for the period 1966 up to October 2013. The population had to be ≥65 years of age and had to have undergone urethral sling procedures, periurethral injection of bulking agents, artificial urinary sphincter surgery, bladder injection treatment with onabotulinumtoxin A or sacral neuromodulation treatment. Eligible outcomes were episodes of incontinence/urine leakage, adverse events, and quality of life.The studies included had to be at a moderate or low risk of bias. Mean difference (MD) or standard mean difference (SMD)as well as risk difference (RD) and the 95 % CI were calculated.Results: Five studies-all on the suburethral sling procedure in women- that fulfilled the inclusion criteria were identified. The proportion of patients reporting persistent SUI after surgery ranged from 5.2 to 17.6 %. One study evaluating quality of life (QoL) showed a significant improvement after surgery. The complication rates varied between 1 and 26 %, mainly bladder perforation, bladder emptying disturbances, and de novo urge.Conclusion: The suburethral sling procedure improves continence as well as QoL among elderly women with SUI; however, evidence is limited.
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| 3. |
- Guo, Jinan, et al.
(författare)
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Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available.Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups.Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892-0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935-0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1-3 cancer subgroups.Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.
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| 4. |
- H Jonsson, Magnus, et al.
(författare)
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Markers of renal function at admission and mortality in hip fracture patients-a single center prospective observational study
- 2021
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:3, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- Plasma cystatin C and shrunken pore syndrome (SPS) are associated with increased mortality in older adults. The objective was to assess the association between these markers of kidney function at admission and mortality in hip fracture patients. Hip fracture patients presenting at Lund University Hospital were eligible for inclusion. Cox regression was used to assess association between plasma cystatin C, creatinine, cystatin C- or creatinine-based estimations of glomerular filtration rate (eGFR(CYS) and eGFR(CREA)), or SPS (defined as eGFR(CYS)/eGFR(CREA) < 0.7) and mortality during one year follow up. Improvement in discrimination relative to the Nottingham Hip fracture score was assessed by Receiver Operational Characteristics (ROC) analysis and calculation of Net Reclassification Index (NRI). 996 patients were included in the study. Cystatin C, creatinine, eGFR(CYS) and eGFR(CREA) were associated with one-year mortality in both unadjusted and adjusted analyses. The association with mortality was stronger for cystatin C and for eGFR(CYS) than for creatinine and eGFR(CREA). Patients with SPS had doubled mortality compared with patients without SPS (43.7 and 20.2%, respectively, p < .001). Hazard ratio for SPS in the adjusted analysis was 1.66 (95%CI; 1.16-2.39, p = .006). None of the markers improved discrimination compared to the Nottingham Hip Fracture Score using ROC analysis whereas eGFR(CYS) and eGFR(CREA) improved NRI. Our conclusion is that plasma concentrations of creatinine or cystatin C, eGFR(CYS) or eGFR(CREA) or SPS at admission in hip fracture patients are associated with mortality when known risk factors are accounted for. Identification of high risk patients may be improved by eGFR(CYS) or eGFR(CREA).
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| 5. |
- Samuelsson, Eva, et al.
(författare)
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Effect of pharmacological treatment for urinary incontinence in the elderly and frail elderly: A systematic review
- 2015
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Ingår i: Geriatrics & Gerontology International. - : Wiley. - 1444-1586 .- 1447-0594. ; 15:5, s. 521-534
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The prevalence and severity of urinary incontinence (UI) increase with age and comorbidity. The benefits of pharmacotherapy for UI in the elderly are questionable. The aim of the present study was to systematically review the efficacy of pharmacological treatment for UI in the elderly and frail elderly. Methods: We searched PubMed, EMBASE, Cochrane library and Cinahl databases through October 2013 to identify prospective controlled trials that evaluated pharmacological treatment for UI in persons aged >= 65 years. Elderly persons living in nursing homes were regarded as frail elderly. Outcomes were urinary leakage, quality of life and adverse events. Results: We screened 1038 abstracts and assessed 309 full-text articles. We identified 13 trials of high or moderate quality; 11 evaluated anticholinergic drugs and two evaluated duloxetine. Oxybutynin, the only drug studied in the frail elderly population, had no effect on urinary leakage or quality of life in elderly with urgency UI (UUI). Seven trials evaluated the effects of darifenacin, fesoterodine, solifenacin, tolterodine or trospium. Urinary leakage decreased (standard mean difference: -0.24, 95% confidence interval -0.32-0.15), corresponding to a reduction of half a leakage per 24 h. Common side-effects of treatment were dry mouth and constipation. Data were insufficient for evaluation of the effect on quality of life or cognition. The evidence was insufficient to evaluate the effects of duloxetine. No eligible studies on mirabegron and estrogen were found. Conclusions: Anticholinergics have a small, but significant, effect on urinary leakage in older adults with UUI. Treatment with drugs for UUI in the frail elderly is not evidence based.
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| 6. |
- Harris, Anna E., et al.
(författare)
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Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.
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| 7. |
- Löfgren, Annica, et al.
(författare)
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Women's experience of sexuality after radical cystectomy : a qualitative study
- 2023
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 57:1-6, s. 24-28
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to explore how women experienced sexuality after radical cystectomy due to bladder cancer.METHODS: We performed an interview study with qualitative design with content analysis. Inclusion criteria were age below 75 years. In total 10 women, with a median age of 64 years at surgery, were interviewed at median 24 months post radical cystectomy.RESULTS: The 10 women described sexual life as affected after surgery but they all tried to find ways to overcome the new situation together with their partner. The overall theme was 'A balance between emotional and physical closeness' emerged from 30 codes that were condensed into five subcategories and two categories: 'A sensual relationship' and 'A sexual relationship'. The first category constituted the subcategories 'Feeling of intimacy' and 'The importance of the relationship'. The category 'A sexual relationship' was revealed from the subcategories 'Reluctance to engage in sexual activity' and 'Partner inability to engage in sexual activity', and 'Acting for sexual rehabilitation'.CONCLUSIONS: The uncertainty that the women felt about their anatomical changes after radical cystectomy created a sexual anxiety and reluctance to resume intercourse. Even though the surgery had a major impact on their sexual life, the women tried to be sexually active. However, the meaning of sexual life was not just having sexual activity but also included closeness, affirmation, affection, and feeling attractive. Sexual counseling at an appropriate timepoint is essential to assure a balance between emotional and physical closeness, i.e. to regain sexual health.
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| 8. |
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| 9. |
- Stenzelius, Karin, et al.
(författare)
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Catheter-associated urinary tract infections and other infections in patients hospitalized for acute stroke : A prospective cohort study of two different silicone catheters
- 2016
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Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 50:6, s. 483-488
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection. The primary aim of this study was to investigate whether the use of a silicone catheter coated with an ultrathin layer of a combination of the noble metals gold, palladium and silver (BIPTM-silicone catheter) could reduce the incidence of CAUTI and antibiotic prescription compared with a standard silicone catheter in a cohort of acute neurological patients suffering primarily from stroke. At the same time, all infectious events requiring prescription of an antimicrobial agent were registered and are reported. Materials and methods: The study was designed as a crossover cohort study enrolling men and women aged over 18 years, requiring emergency management for stroke including the insertion of an indwelling catheter. Data on patient characteristics, urinary tract infections (UTIs), other infectious events and all antibiotic prescriptions were recorded prospectively. Results: The patients' characteristics differed in the two centres in terms of age but not in diagnosis distribution. UTIs were recorded in 78 (24.2%) of the patients, ahead of pulmonary tract infections (n = 65; 20.2%). There was no difference in terms of CAUTI in the two catheter groups, even in subgroups with catheter treatment for 1 week or less. The patients with a diagnosed UTI required 3.5 more days of hospitalization than those without a UTI. Conclusion: CAUTIs were the most frequent healthcare-associated infections, slightly ahead of pulmonary tract infections. No advantages of the coated catheter could be found in this cohort of critically ill patients.
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| 10. |
- Lind, Anna Karin, et al.
(författare)
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Health-related quality of life prior to and 1 year after radical cystectomy evaluated with FACT-G and FACT-VCI questionnaires
- 2023
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 58:1, s. 76-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate health-related quality of life (HRQoL) before and 1 year after radical cystectomy in relation to age and gender.METHODS: This prospective study involves 112 men and 40 women with bladder cancer treated with radical cystectomy between 2015 and 2018. HRQoL was assessed preoperatively and 1 year post-surgery through Functional Assessment of Cancer Therapy Scale - General (FACT-G) and Functional Assessment of Cancer Therapy Scale - Vanderbilt Cystectomy Index (FACT-VCI) questionnaires. The median age of the 152 patients was 71.5 years.RESULTS: Preoperatively, emotional and functional well-being were negatively affected. Physical, emotional and functional well-being presented higher values 1 year after surgery compared to before radical cystectomy, that is, better HRQoL. Social well-being showed a reduction, especially regarding closeness to partner and support from family. Men and women were equally satisfied with their sex life before radical cystectomy, but less so 1 year after, where men were less satisfied compared to women. Additionally, one out of five patients reported that they had to limit their physical activities, were afraid of being far from a toilet and were dissatisfied with their body appearance after surgery.CONCLUSIONS: Recovery regarding HRQoL was ongoing 1 year after radical cystectomy. Patients recovered in three out of four dimensions of HRQoL, but social well-being was still negatively affected 1 year after treatment. Sexual function after radical cystectomy was exceedingly limited for both men and women. An individual sexual rehabilitation plan involving the couple with special intention to encourage intimacy, might not only improve sexual life but also have a positive effect on social well-being as a consequence.
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