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Owing to the improvements in detection, diagnostics, and treatment, many men currently diagnosed with prostate cancer (PCa) have a low risk of PCa death. For many men PCa has become a chronic disease with a small risk of progression that remains even decades after date of diag-nosis. In this thesis PCa was used as an example of a chronic disease, since it holds all the main characteristics required by the WHO definition of a chronic disease. Against this background, the aim of this PhD thesis was to create models that can be used to quantify the probability of dif-ferent treatment trajectories and to assess the duration of certain disease states, while accounting for patient characteristics, disease severity, and primary treatment. In Paper I a state transition model was developed for prediction of dis-ease trajectories. The developed state transition model showed good consistency with a follow-up spanning up to 30 years. In Paper II a state transition model was developed and validated using age, Charlson comorbidity index, and a drug comorbidity index (DCI) based on filled drug prescriptions collected at a population-based level to estimate life expectancy. In Paper III the state transition model proposed in Paper I was used to assess 30-year PCa trajectories in men managed with active surveillance, in order to identify the ideal candidates for this management strategy. In Paper IV the state transition model from Paper I was updated includ-ing the castration resistant PCa (CRPC) state as an additional state and estimating the duration of the CRPC state as well as its outcomes. In Paper V, the updated state transition model from Paper IV was used to model long term outcomes for men with PCa managed with watchful waiting (WW). Since WW is currently recommended for men with PCa and life expectancy less than 10 years, the state transition model from Paper II was used to estimate life expectancy.

Introduction Kidney stone disease is a common disease with high recurrence rates. Sufficient intake of water is the cornerstone in primary prevention of stone disease. However, the mineral composition of water can affect urinary minerals and influence stone formation. The aim of this study is to assess the variation in the mineral composition of bottled sparkling or carbonated drinking water across Europe. Material and methods The two largest supermarket chains in each participating country were visited to obtain data on mineral composition regarding bicarbonate, calcium, magnesium, potassium, sodium and sulphates of sparkling or carbonated waters by reading the ingredient labels on the bottles supplied by the manufacturers. Alternatively, the web-shops of these supermarkets were consulted. Results In total, 126 sparkling water brands across ten European countries were analysed regarding mineral composition. The median concentrations per mineral varied greatly. The greatest variation in median mineral content was found for sodium and sulphates with levels ranging from 3.1 mg/l to 63.0 mg/l and 6.0 mg/l to 263.0 mg/l respectively. A wide distribution of calcium content was found in Switzerland, with calcium levels reaching up to 581.6 mg/l. Conclusions This study confirms that the mineral composition of sparkling or carbonated water varies greatly across Europe. Patients with kidney stone disease should be aware that the mineral content of water may influence stone formation and be mindful of the great variation that exists between different water brands. Mineral water can be a source of potential promotors or inhibitors of stone formation and patients and urologists need to be mindful of this.

Kidney stone disease (KSD) is a complex disease. Besides the high risk of recurrence, its association with systemic disorders contributes to the burden of disease. Sufficient water intake is crucial for prevention of KSD, however, the mineral content of water might influence stone formation, bone health and cardiovascular (CVD) risk. This study aims to analyse the variations in mineral content of bottled drinking water worldwide to evaluate the differences and describes the possible impact on nephrological and urological diseases. The information regarding mineral composition (mg/L) on calcium, bicarbonate, magnesium, sodium and sulphates was read from the ingredients label on water bottles by visiting the supermarket or consulting the online shop. The bottled waters in two main supermarkets in 21 countries were included. The evaluation shows that on a global level the mineral composition of bottled drinkable water varies enormously. Median bicarbonate levels varied by factors of 12.6 and 57.3 for still and sparkling water, respectively. Median calcium levels varied by factors of 18.7 and 7.4 for still and sparkling water, respectively. As the mineral content of bottled drinking water varies enormously worldwide and mineral intake through water might influence stone formation, bone health and CVD risk, urologists and nephrologists should counsel their patients on an individual level regarding water intake.

To evaluate whether the position of the working channel affects the effectiveness of flexible ureteroscopy.

OBJECTIVES: To assess the use of post radical prostatectomy (RP) urinary incontinence (PPI) surgery and to investigate factors related to its use. METHODS: Cohort study in Prostate Cancer database Sweden (PCBaSe) of men who underwent primary RP between 1998 and 2012. PPI correction procedures were identified in the Patient Registry. Hazard ratios (HR) and 95% confidence intervals (CIs) of PPI surgeries were estimated. RESULTS: Seven hundred eighty-two out of 26 280 (3%) men underwent PPI surgery at a median time of 3 years after RP. There was an eightfold increase in the absolute number of PPI surgeries during 2000-2014 and a threefold increase in the number per 1000 RPs performed. Factors associated with high use PPI surgery were age >70, HR 1.96 (1.54-2.50), and high hospital RP volume (>100 RPs/year), HR 0.81 (0.66-0.99). There was a 10-fold difference in use of PPI surgery per 1000 RPs between the county with the highest versus lowest use. In a subgroup of men with Patient-Reported Outcome Measures (PROM); severe PPI was reported by 7% of men and 24% of them underwent PPI surgery. CONCLUSIONS: Three percent of all men received PPI surgery, with a 10-fold variation among health care providers. Only a quarter of men with severe PPI underwent PPI surgery, suggesting that PPI surgery remains underutilized.

Detailed specifications of the model, including states, transitions, and transition probabilities. (DOCX 45 kb)

Supplementary figures and tables. (DOCX 212 kb)

The US Food and Drug Administration recently announced the need to evaluate the association between PDE5is and melanoma. We performed a meta-analysis on the association between PDE5i and melanoma using random effects models and examined whether it met Hill's criteria for causality. A systematic search of Medline, EMBASE, and the Cochrane Library from 1998 to 2016 identified three case-control studies and two cohort studies, including a total of 866 049 men, of whom 41 874 were diagnosed with melanoma. We found a summary estimate indicating an increased risk of melanoma in PDE5i users (relative risk = 1.12, 95% confidence interval = 1.02 to 1.23). However, there was no difference in risk between men with low and high exposure to PDE5i, and risk was higher for in situ melanoma than localized and high-risk melanoma, suggesting a lack of dose response and biological gradient. PDE5i use was also associated with basal cell cancer, suggesting a lack of specificity and likely confounding by ultraviolet exposure. Thus, although this meta-analysis found a statistically significant association between PDE5i and melanoma, it did not satisfy Hill's criteria for causality. Correction: https://doi.org/10.1093/jnci/djx156

BACKGROUND: Controversial results have shown a significant association with either low or high total testosterone (tT) levels and high risk prostate cancer (PCa). We tested the relationship between circulating tT and grade group 5 (G5) PCa at radical prostatectomy (RP) in patients with preoperative low- to intermediate-risk disease. METHODS: Serum sex hormones were assessed the day before RP in a cohort of 846 patients with low- to intermediate-risk PCa. Patients were segregated using the new 5-tiered Gleason grade groups. Restricted cubic spline functions and logistic regression analyses tested the association between sex hormones and G5 PCa. Differences in potential predictive accuracy (PA) were assessed for tT and prostate-specific antigen (PSA) levels. RESULTS: Overall, 27 men (3.2%) had G5 PCa at RP, and this group had higher PSA values than patients with G1–G4 PCa (P = 0.02). The groups did not differ in terms of preoperative mean hormonal values. Both low and high circulating tT values depicted a nonlinear U-shaped correlation with G5 PCa at RP. The lowest and highest (10th and 90th percentiles) tT values and biopsy PCa grade emerged as multivariable independent predictors of G5 PCa at RP (all P < 0.05). PA for G5 PCa did not differ between tT (area under the curve [AUC] 0.631) and PSA (AUC 0.636). CONCLUSIONS: Circulating tT was a significant predictor of G5 PCa at RP in patients with preoperative low- to intermediate-risk disease. Preoperative tT and PSA values showed similar PA for the most aggressive disease, confirming a potential role for circulating androgens in preoperative risk assessment of PCa patients. Prostate 77:234–241, 2017. © 2016 Wiley Periodicals, Inc.

Patients with high socioeconomic status (SES) have better cancer outcomes than patients with low SES. This has also been shown in Sweden, a country with tax-financed health care aiming to provide care on equal terms to all residents. The association between income and educational level and diagnostics and treatment as outlined in national guidelines and prostate cancer (Pca) and all-cause mortality was assessed in 74,643 men by use of data in the National Prostate Cancer Register of Sweden and a number of other health care registers and demographic databases. In multivariable logistic regression analysis, men with high income had higher probability of Pca detected in a health-check-up, top versus bottom income quartile, odds ratio (OR) 1.60 (95% CI 1.45-1.77) and lower probability of waiting more than 3 months for prostatectomy, OR 0.77 (0.69-0.86). Men with the highest incomes also had higher probability of curative treatment for intermediate and high-risk cancer, OR 1.77 (1.61-1.95) and lower risk of positive margins, (incomplete resection) at prostatectomy, OR 0.80 (0.71-0.90). Similar, but weaker associations were observed for educational level. At 6 years of follow-up, Pca mortality was modestly lower for men with high income, which was statistically significant for localized high-risk and metastatic Pca in men with no comorbidities. All-cause mortality was less than half in top versus bottom quartile of income (12% vs. 30%, p