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This post-authorization safety study (EU PAS Register Number: EUPAS16088) was designed to compare the incidence of cancer outcomes in patients treated with mirabegron versus antimuscarinic medications. Cohorts of mirabegron initiators during 2012–2018 were propensity-score matched to antimuscarinic medication initiators within real-world data sources (Danish National Registers, Swedish National Registers, Clinical Practice Research Datalink [UK], Optum [US], and Humana [US]). Incident cancer cases were identified during follow-up from direct linkage to cancer registers or validated through medical record review or through physician questionnaires. Comparisons of sex-specific composite cancer outcomes (cancer of the lung/bronchus, colon/rectum, melanoma of skin, urinary bladder, non-Hodgkin lymphoma, kidney/renal pelvis, pancreas, prostate in men and breast and uterus in women) were made overall and for person-time in the first year and after the first year following start of treatment, for all ages and for the subgroup ≥65 years. Among the 80,637 mirabegron initiators matched to 169,885 antimuscarinic medication initiators, 68% were at least 65 years of age and 66% were women. Over 5000 incident cancer cases were observed overall. Incidence rates were higher for men than women for composite and individual cancer outcomes. The pooled fixed effects hazard ratios for composite cancer outcomes (all ages) were 1.05 (95% confidence interval [CI]: 0.98–1.14) for women and 1.06 (95% CI: 0.98–1.14) for men. Results were similar in persons ≥65 years. The results suggest no association between mirabegron use and risk of cancer, compared with antimuscarinic medications, in either men or women. Registration: EU PAS Register Number: EUPAS16088 [ABSTRACT FROM AUTHOR]

Background: Metastatic urothelial cancer (UC) is the eighth most common cause of cancer death in the UK. Standard first-line treatment, for most patients, is cytotoxic chemotherapy. Although UC is initially sensitive to chemotherapy, relapse is almost inevitable and outcomes are poor; median overall survival is 8 months. Therefore, there is an urgent need for novel therapies to improve outcomes for this patient group.Methods: ATLANTIS is a randomised phase II umbrella-design screening trial of maintenance therapy in biomarker-defined subgroups of patients with advanced UC. The primary end point is progression-free survival, and the study involves over 30 UK cancer centres.Discussion: ATLANTIS is the first study in the UK to employ a precision-medicine approach to patients with UC for maintenance treatment. Agents with a positive efficacy signal will proceed to randomised phase III trials to confirm the activity of novel, biologically stratified therapies in UC.Registration: ATLANTIS trial EudraCT number 2015-003249-25. ISRCTN25859465. [ABSTRACT FROM AUTHOR]

Purpose: To report the outcomes of paediatric ureteroscopy (URS) for stone disease from a specialist endourology centre in the UK. Ureteroscopy for management of stone disease has increased worldwide and is now being done more commonly in the paediatric age group. Methods: Data were analysed retrospectively from a database maintained between April 2010 and May 2018. Consecutive patients ≤ 16 years of age undergoing semi-rigid or flexible URS for stone disease were included. Stone size and stone-free rate (SFR) were routinely assessed using an ultrasound (USS) and/or plain KUB XR. Complications were graded according to the Clavien–Dindo classification and recorded within 30 days post-procedure and readmissions within 90 days after the procedure were also captured. Results: Over the 8-year period between April 2010 and April 2018, 81 patients with a mean age of 8.8 years (range 18 months–16 years) and a male to female ratio 1:1.1 underwent 102 procedures (1.28 procedure/patient to be stone free). Of the 81 patients, 29 (35.8%) had comorbidities, with 26 (32%) having multiple comorbidities. The mean (± SEM) single and overall stone size was 9.2 mm (± 0.48, range 3–30 mm) and 11.5 mm (± 0.74, range 4–46 mm) respectively, with 22 (27.1%) having multiple stones. Thirty-five (34.7%) had stent in situ pre-operatively. The stone location was in the ureter (26.6%), lower pole (35.4%), and renal pelvis (16.5%), with 22/81(27%) having multiple stones and 21/102 (20.5%) where a ureteral access sheath (UAS) was used. With a mean hospital stay of 1.2 days, the initial and final SFR was 73% and 99%, respectively, and 61/102 (60%) had ureteric stent placed at the end of the procedure. While there were no intra-operative complications, the readmission rate was less than 1% and there were only three early complications recorded. This included a case each of prolonged admission for pain control (grade I), urinary retention (grade II) and post-operative sepsis requiring a brief ITU admission (grade IV). Conclusion: Our study demonstrates that in appropriate setting a high stone-free rate can be achieved with minimal morbidity for paediatric patients. There is potentially a need to factor the increasing role of URS in future paediatric urolithiasis guidelines. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a growing contributor to the global burden of noncommunicable diseases. Early diagnosis and treatment can reduce the severity of kidney damage and the need for dialysis or transplantation. It is not known whether mild-to-moderate renal pelvis dilatation (RPD) identified at 18-20 weeks gestation is an early indicator of renal pathology. The aim of this follow-up to the Welsh Study of Mothers and Babies was to assess the risk of hospital admission in children with mild-to-moderate antenatal RPD compared with children without this finding. We also examined how the natural history of the RPD (whether the dilatation persists in later pregnancy or postpartum) or its characteristics (unilateral versus bilateral) changed the risk of hospital admission.Methods/findings: This population-based cohort study included singleton babies born in Wales between January 1, 2009, and December 31, 2011 (n = 22,045). We linked ultrasound scan data to routinely available data on hospital admissions from the Patient Episode Database for Wales (PEDW). The outcome was a hospital admission for urinary tract causes (defined by an expert study steering group) in the first three years of life. We used Cox regression to model time to first hospital admission, according to whether there was evidence of RPD at the fetal anomaly scan (FAS) and/or evidence of dilatation in later investigations, adjusting for other predictors of admission. We used multiple imputation with chained equations to impute values for missing data. We included 21,239 children in the analysis. The risk of at least one hospital admission was seven times greater in those with RPD (n = 138) compared with those without (n = 21,101, conditional hazard ratio [cHR] 7.23, 95% confidence interval [CI] 4.31-12.15, p < 0.001). The risk of hospital admission was higher in children with RPD at the FAS and later dilatation (cHR 25.13, 95% CI 13.26-47.64, p < 0.001) and in children without RPD at the FAS who had later dilatation (cHR 62.06, 95% CI 41.10-93.71, p < 0.001) than in children without RPD (n = 21,057). Among children with RPD at the FAS but no dilatation in later pregnancy or postpartum, we did not find an association with hospital admissions (cHR 2.16, 95% CI 0.69-6.75, p = 0.185), except when the initial dilatation was bilateral (cHR 4.77, 95% CI 1.17-19.47, p = 0.029). Limitations of the study include small numbers in subgroups (meaning that these results should be interpreted with caution), that less severe outcomes (such as urinary tract infections [UTIs] managed in the community or in outpatients) could not be included in our analysis, and that obtaining records of radiological investigations later in pregnancy and postpartum was challenging. Our conclusions were consistent after conducting sensitivity analyses to account for some of these limitations.Conclusions: In this large population-based study, children with RPD at the FAS had higher rates of hospital admissions when there was persistent dilatation in later pregnancy or postpartum. Our results can be used to improve counselling of parents and develop care pathways for antenatal screening programmes, including protocols for reporting and further investigation of RPD. [ABSTRACT FROM AUTHOR]