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Objective: Lower urinary tract symptoms (LUTS) are becoming more prevalent in the ageing population of males living with HIV. Drugs to treat LUTS are known for both their potential role as victims in drug–drug interactions (DDIs) and their side effects. We aimed to evaluate the current use of drugs to treat LUTS and to assess potential DDIs in our cohort of adult males living with HIV. Design: This was a retrospective review of pharmacy records. Methods: We recorded the combination antiretroviral therapy (cART) regimen and any use of drugs to treat LUTS (anatomical therapeutic chemical codes G04CA/CB/CX and G04BD). Potential DDIs were assessed using the interaction checker developed by the University of Liverpool (https://www.hiv-druginteractions.org/checker). Results: A total of 411 adult males living with HIV were included in this analysis. The median (interquartile range [IQR]) age was 53 (41–62) years. Nineteen (4.6%) patients used one or more drugs to treat LUTS. As expected, older patients were more likely to be receiving treatment for LUTS: Q1 (20–40 years) = 0%; Q2 (41–52 years) = 2%; Q3 (53–61 years) = 7%; Q4 (62–79 years) = 10%. Seven potential DDIs between cART and LUTS treatment were noted in six of the 19 (32%) patients. Following medication reviews of these six patients, the following interventions were proposed: evaluate safe use of alpha‐blocker (n = 4), change in cART (n = 2), and dose reduction of the anticholinergic agent (n = 1). Conclusion: Treatment for LUTS coincided with cART in 7%–10% of patients aged above the median age of 53 years in our cohort. Improvements in DDI management appeared to be possible in this growing cohort of males living with HIV and with LUTS. [ABSTRACT FROM AUTHOR]

In this study, the thermal and mechanical behaviors were investigated by simulating laser remelting of atmospheric plasma‐sprayed yttria‐stabilized zirconia coatings, and the molten depth and regions of stress concentration were compared between simulation and experiment. The heat treatment process of the remelted coating was also simulated. The crack formation mechanism in the YSZ coating remelted by laser and the heat‐treatment effect on residual stress were investigated. Results showed that the simulated results were consistent with the experimental measurements, and the residual thermal stress was the main cause of cracks formation. The coating remelted by a laser power of 1500 W and a scanning rate of 9 mm/s possessed less residual concentrated stress and segmented cracks. Heat treatment released concentrated stress, which was still accurate for the ceramic coating. If the coatings were slowly heated to demonstrate heat treatment after laser remelting, the cracks in the remelted layer decreased correspondingly. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of α‐blockers compared to standard therapy or placebo for ureteric stones of ≤10 mm confirmed by imaging in adult patients presenting with symptoms of ureteric stone disease. Patients and Methods: We performed a systematic search in multiple databases and grey literature with no restrictions on the language of publication or publication status, up until November 2017. We included randomised controlled trials evaluating ureteric stone passage in adult patients that compared α‐blockers with standard therapy or placebo. Two review authors were independently responsible for study selection, data extraction, and risk‐of‐bias assessment. We performed a meta‐analysis using a random‐effect model. The quality of evidence was assessed on outcome basis according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results: We included 67 studies, with 10 509 participants overall. Of these, 15 studies with 5 787 participants used a placebo. Stone clearance: treatment with an α‐blocker may result in a large increase in stone clearance (risk ratio [RR] 1.45, 95% confidence interval [CI] 1.36–1.55; low‐quality evidence), corresponding to 278 more (95% CI: 223–340 more) stone clearances per 1 000 participants. For major adverse events, treatment with an α‐blocker may have little effect (RR 1.25, 95% CI: 0.80–1.96; low‐quality evidence), which corresponds to five more (95% CI four fewer to 19 more) major adverse events per 1 000 participants. Patients treated with α‐blockers may also experience shorter stone expulsion times (mean difference [MD] −3.40 days, 95% CI: −4.17 to −2.63; low‐quality evidence), use less diclofenac (MD −82.41 mg, 95% CI: −122.51 to −42.31; low‐quality evidence) and likely require fewer hospitalisations (RR 0.51, 95% CI: 0.34–0.77; moderate‐quality evidence). Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI: 0.53–1.02; low‐quality evidence). Based on a pre‐defined subgroup analysis (test for subgroup difference, P = 0.002), there may be a different effect of α‐blockers based on stone size with RRs of 1.06 (95% CI: 0.98–1.15; P = 0.16; I² = 62%) for stones of ≤5 mm vs 1.45 (95% CI: 1.22–1.72; P < 0.0001; I² = 59%) for stones of >5 mm. We did not find evidence for possible subgroup effects based on stone location or α‐blocker type. Conclusions: In patients with ureteric stones, α‐blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that α‐blockers may be less effective in smaller (≤5 mm) than larger stones (>5 mm). [ABSTRACT FROM AUTHOR]

Objective: To develop an evidence‐based recommendation concerning the use of α‐blockers for uncomplicated ureteric stones based on an up‐to‐date Cochrane review, as the role of medical expulsive therapy for uncomplicated ureteric stones remains controversial in the light of new contradictory trial evidence. Methods: We applied the Rapid Recommendations approach to guideline development, which represents an innovative approach by an international collaborative network of clinicians, researchers, methodologists and patient representatives seeking to rapidly respond to new, potentially practice‐changing evidence with recommendations developed according to standards for trustworthy guidelines. Results: The panel suggests the use of α‐blockers in addition to standard care over standard care alone in patients with uncomplicated ureteric stones (weak recommendation based on low‐quality evidence). The panel judged that the net benefit of α‐blockers was small and that there was considerable uncertainty about patients' values and preferences. This means that the panel expects that most patients would choose treatment with α‐blockers but that a substantial proportion would not. This recommendation applies to both patients in whom the presence of ureteric stones is confirmed by imaging, as well as patients in whom the diagnosis is made based on clinical grounds only. Conclusion: The Rapid Recommendations panel suggests the use of α‐blockers for patients with ureteric stones. Shared decision‐making is emphasised in making the final choice between the treatment options. [ABSTRACT FROM AUTHOR]

Study Type - Diagnosis (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? The European Randomized study of Screening for Prostate Cancer (ERSPC) showed a reduction in prostate cancer mortality of 21% for PSA-based screening at a median follow-up of 11 years. In the ERSPC, men are screened at 4-year intervals. A prostate biopsy is recommended for men with a PSA level ≥3.0 ng/mL. The study shows that the positive predictive value (PPV) of a prostate biopsy indicated by PSA-based screening remains equal throughout consecutive screening rounds in men without a previous biopsy. In men who have previously had a benign biopsy, the PPV drops considerably, but 20% of the cancers detected still show aggressive characteristics. OBJECTIVE To assess the positive predictive value (PPV) of prostate biopsy, indicated by a prostate-specific antigen (PSA) threshold of ≥3.0 ng/mL, over time, in the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC)., PATIENTS AND METHODS In the Rotterdam section of the ERSPC, a total of 42 376 participants, aged 55-74 years, identified from population registries were randomly assigned to a screening or control arm., For the ERSPC men undergo PSA screening at 4-year intervals. A total of three screening rounds were evaluated; therefore, only men aged 55-69 years at the first screening were eligible for the present study., RESULTS PPVs for men without previous biopsy remained equal throughout the three subsequent screenings (25.5, 22.3 and 24.8% respectively)., Conversely, PPVs for men with a previous negative biopsy dropped significantly (12.0 and 15.2% at the second and third screening, respectively)., Additionally, in men with and without previous biopsy, the percentage of aggressive prostate cancers (clinical stage >T2b, Gleason score ≥7) decreased after the first round of screening from 44.4 to 23.8% in the second ( P < 0.001) and 18.6% in the third round ( P < 0.001)., Repeat biopsies accounted for 24.6% of all biopsies, but yielded only 8.6% of all aggressive cancers., CONCLUSIONS In consecutive screening rounds the PPV of PSA-based screening remains equal in previously unbiopsied men., In men with a previous negative biopsy the PPV drops considerably, but 20% of cancers detected still show aggressive characteristics., Individualized screening algorithms should incorporate previous biopsy status in the decision to perform a repeat biopsy with the aim of further reducing unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long-term outcomes among men with clinically-detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen-detected prostate cancer. OBJECTIVE To examine the long-term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC)., PATIENTS AND METHODS Among 42 376 men randomised during the period of the first round of the trial (1993-1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively., Of these men, 420 (36.5%) screen-detected and 54 (25.7%) controls underwent RP with long-term follow-up data (median follow-up 9.9 years)., Progression-free (PFS), metastasis-free (MFS) and cancer-specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen-detected (vs control) was associated with RP outcomes after adjusting for standard predictors., RESULTS RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen-detected cases had significantly lower prostate-specific antigen (PSA) levels at diagnosis., Men from the screening arm had a significantly higher PFS ( P= 0.003), MFS ( P < 0.001) and CSS ( P= 0.048)., In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.83, P= 0.011) and metastasis (HR 0.18, 95% CI 0.06-0.59, P= 0.005)., Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms., Limitations of the present study include lead-time bias and non-randomised treatment selection., CONCLUSIONS After RP, screen-detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow-up time., The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables., However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Active surveillance aims to reduce overtreatment by selecting patients with low risk prostate cancer (PCa) based on favourable disease characteristics. However, most studies on active surveillance do not have long-term results available; in particular, data on patients with intermediate risk disease are lacking. Our findings demonstrate that withholding radical treatment in men with low or intermediate risk screen-detected localized PCa leads to a substantial delay or even avoidance of radical treatment in a majority of men. Favourable disease-specific outcomes confirm the feasibility of active surveillance for low risk PCa and also support a role for active surveillance in selected patients with intermediate risk PCa. OBJECTIVE To assess the longer-term feasibility of active surveillance, we aimed to evaluate outcomes of patients with screen-detected localized prostate cancer (PCa) who initially elected to withhold radical treatment for either low or intermediate risk disease., PATIENTS AND METHODS All men underwent screening for PCa in the Rotterdam and Helsinki arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC); eligible men were diagnosed with PCa prior to the establishment of the ERSPC-affiliated Prostate Cancer Research International: Active Surveillance (PRIAS) study (1994-2007) and were initially expectantly managed in the absence of a fixed follow-up protocol., Low risk PCa was defined as clinical stage T1/T2, PSA ≤ 10 ng/mL, PSA density < 0.2 ng/mL/mL, Gleason ≤ 6 and maximum two positive biopsy cores, whereas PSA 10-20 ng/mL, Gleason score 7 and three positive biopsy cores were considered intermediate risk features., Disease-specific, overall and treatment-free survival were analysed using the Kaplan-Meier and competing risks methods., RESULTS In all, 509 patients with PCa were eligible, of whom 381 were considered low risk and 128 intermediate risk., During a median follow-up of 7.4 years, a total of 221 patients (43.4%) switched to deferred treatment after a median of 2.6 years., The calculated 10-year disease-specific survival rates were 99.1% and 96.1% for low and intermediate risk patients, respectively ( P= 0.44), and for overall survival 79.0% and 64.5%, respectively ( P= 0.003)., Competing risks analysis showed similar results., CONCLUSIONS Withholding radical treatment in men with low to intermediate risk screen-detected PCa leads to a substantial delay or even avoidance of radical treatment and its potential side-effects in a majority of patients., Disease-specific outcomes at 7.4 years of follow-up are favourable in low as well as intermediate risk patients., This confirms the feasibility of active surveillance according to contemporary criteria, and also suggests a potential role for active surveillance in selected men with intermediate risk features. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (case control) Level of Evidence 3a What's known on the subject? and What does the study add? Treatment of advanced PC might put patients at an increased risk of cardiovascular events. Recent studies have suggested that the excess mortality is lower among men who were diagnosed with screen detected PC in comparison to men with clinically diagnosed PC, possibly due to the use of medications for cardiovascular disease and the change to a healthier lifestyle of men with a screen detected PC. Men with clinically diagnosed PC have an increased risk of death unrelated to PC itself, i.e., the excess mortality is based on an increased risk of dying from other neoplasm and diseases of the circulatory or respiratory system. OBJECTIVE To assess the cause-specific mortality unrelated to prostate cancer (PC) itself in patients with screen- and clinically diagnosed PC., PATIENTS AND METHODS The present study was conducted among participants of the European Randomized Study of Screening for Prostate Cancer., Based on consensus of the causes of death committee (CODC), all patients who died from PC were excluded., In the intervention arm, cases were patients with a screen-detected PC, aged 55-74 years, between 1993 and 2001., These cases were matched to two controls in whom no cancer was found after biopsy, and two controls in whom no cancer was suspected after screening. In the control arm, cases were patients with clinically diagnosed PC, aged 55-74 years, between 1993 and 2001. These cases were matched to four controls without PC. Matching was done with respect to date of birth, screening and/or diagnosis. Men were followed up to 31 December 2007., RESULTS No statistically significant difference in overall mortality between cases and controls in the intervention arm was observed: relative risk (RR) 1.26 (95% confidence interval [CI] 0.96-1.65; P = 0.102) and RR 1.13 (95% CI 0.86-1.47; P = 0.381)., In the control arm, the overall mortality was statistically significantly higher in cases relative to controls: RR 1.43 (95% CI 1.03-2.00; P = 0.033)., This difference was because of an increased risk of dying from neoplasms and disease of the circulatory or respiratory system among cases: RR 1.61 (95% CI 1.12-2.29; P = 0.009)., The present study was limited by the relatively small sample size., CONCLUSIONS Increased mortality unrelated to PC itself was observed in men with clinically diagnosed PC, but not in screen-detected PC., The excess mortality in men with clinically diagnosed PC seems to be as a result of a significantly increased risk of dying from neoplasm and disease of the circulatory or respiratory system., Results have to be studied more thoroughly in further clinical trials. [ABSTRACT FROM AUTHOR]

We aim to identify and characterize 'escapes,' men who developed metastasis and/or died from prostate cancer (PCa) despite screening, in the framework of the novel international ESCAPE-project. With this knowledge, the ultimate goal is to improve screening strategy. In this article, we focus on the study cohort of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. In all, 21,210 men were randomized to the screening arm of whom 19,950 were actually screened. The screening interval was 4 years. Men with prostate-specific antigen ≥3.0 ng/ml were recommended to undergo lateralized sextant prostate biopsy. The follow-up was complete until January 1, 2009. Of 19,950 screened men, 2,317 were diagnosed with PCa. Of these cancers 1,946 were detected in a screening round and 371 during an interval. The median follow-up was 11.1 years for the whole cohort and 7.3 years for men diagnosed with PCa. In total, we identified 168 escapes among 2,317 cancers (7.3%) within our screening cohort of 19,950 men (0.8%). More than half of these escapes were found in the initial screening round (94 of 168). Possible mechanisms behind escaping are nonattending, inadequate screening tests, the relative long screening interval, the age cut-off at 75 years, and undertreatment. International cooperation is crucial to compare the escapes of our cohort with other study groups participating in the ESCAPE-project which have different, more aggressive screening strategies. Subsequently, we can achieve improvements of the current screening algorithm, which hopefully will further decrease PCa-specific mortality without increasing overdiagnosis and overtreatment. [ABSTRACT FROM AUTHOR]