Improving Guideline Adherence in Urology

CONTEXT: Clinical practice guidelines (CPGs) distil an evidence base into recommendations. CPG adherence is associated with better patient outcomes. However, preparation and dissemination of CPGs are a costly task involving multiple skilled personnel. Furthermore, dissemination alone does not ensure CPG adherence. Reasons for nonadherence are often complex, but understanding practice variations and reasons for nonadherence is key to improving CPG adherence and harmonising clinically appropriate and cost-effective care. OBJECTIVE: To overview approaches to improving guideline adherence, to provide urology-specific examples of knowledge-practice gaps, and to highlight potential solutions informed by implementation science. EVIDENCE ACQUISITION: Three common approaches to implementation science (the Knowledge-To-Action framework, the Consolidated Framework for Implementation Research, and the Behaviour Change Wheel), are summarised. EVIDENCE SYNTHESIS: Three implementation problems in urology are illustrated: underuse of single instillation of intravesical chemotherapy in non-muscle-invasive bladder cancer, overuse of androgen deprivation therapy in localised prostate cancer, and guideline-discordant imaging in prostate cancer. Research using implementation science approaches to address these implementation problems is discussed. CONCLUSIONS: Urologists, patients, health care providers, funders, and other key stakeholders must commit to reliably capturing and reporting data on patient outcomes, practice variations, guideline adherence, and the impact of adherence on outcomes. Leverage of implementation science frameworks is a sound next step towards improving guideline adherence and the associated benefits of evidence-based care. PATIENT SUMMARY: Clinical practice guideline documents are created by expert panels. These documents provide overviews of the evidence for the tests and treatments used in patient care. They also provide recommendations and it is expected that in most circumstances clinicians will follow these recommendations. Sometimes, health care professionals cannot or do not follow these recommendations and it is not always clear why. In this review article we look at some examples of research approaches to addressing this problem of nonadherence and we provide some examples specific to urology

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features.

Most human papillomavirus (HPV)-independent penile squamous cell carcinomas (PSCCs) originate from an intraepithelial precursor called differentiated penile intraepithelial neoplasia, characterized by atypia limited to the basal layer with marked superficial maturation. Previous studies in vulvar cancer, which has a similar dual etiopathogenesis, have shown that about one fifth of HPV-independent precursors are morphologically indistinguishable from high-grade squamous intraepithelial lesions (HSILs), the precursor of HPV-asssociated carcinomas. However, such lesions have not been described in PSCC. From 2000 to 2021, 55 surgical specimens of PSCC were identified. In all cases, thorough morphologic evaluation, HPV DNA detection, and p16, p53, and Ki-67 immunohistochemical (IHC) staining was performed. HPV-independent status was assigned based on both negative results for p16 IHC and HPV DNA. Thirty-six of the 55 PSCC (65%) were HPV-independent. An intraepithelial precursor was identified in 26/36 cases (72%). Five of them (19%) had basaloid features, morphologically indistinguishable from HPV-associated HSIL. The median age of the 5 patients was 74 years (range: 67 to 83 y). All 5 cases were p16 and DNA HPV-negative. Immunohistochemically, 3 cases showed an abnormal p53 pattern, and 2 showed wild-type p53 staining. The associated invasive carcinoma was basaloid in 4 cases and the usual (keratinizing) type in 1. In conclusion, a small proportion of HPV-independent PSCC may arise on adjacent intraepithelial lesions morphologically identical to HPV-associated HSIL. This unusual histologic pattern has not been previously characterized in detail in PSCC. p16 IHC is a valuable tool to identify these lesions and differentiate them from HPV-associated HSIL

Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX

IMAGINE-IMpact Assessment of Guidelines Implementation and Education : The Next Frontier for Harmonising Urological Practice Across Europe by Improving Adherence to Guidelines

Funding support: The IMAGINE ADT audit is supported by a seeding grant from the EAU Research Foundation.Peer reviewedPostprin

Pathogenesis of Penile Squamous Cell Carcinoma: Molecular Update and Systematic Review.

Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve TP53, CDKN2A, FAT1, NOTCH-1 and PIK3CA. Numerical alterations involve gains in MYC and EGFR, as well as amplifications in HPV integration loci. A few genes including TP53, CDKN2A, PIK3CA and CCND1 harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC

Localized instabilities of the Wigner equation as a model for the emergence of Rogue Waves

In this paper, we model Rogue Waves as localized instabilities emerging from homogeneous and stationary background wavefields, under NLS dynamics. This is achieved in two steps: given any background Fourier spectrum P(k), we use the Wigner transform and Penrose’s method to recover spatially periodic unstable modes, which we call unstable Penrose modes. These can be seen as generalized Benjamin–Feir modes, and their parameters are obtained by resolving the Penrose condition, a system of nonlinear equations involving P(k). Moreover, we show how the superposition of unstable Penrose modes can result in the appearance of localized unstable modes. By interpreting the appearance of an unstable mode localized in an area not larger than a reference wavelength λ0 as the emergence of a Rogue Wave, a criterion for the emergence of Rogue Waves is formulated. Our methodology is applied to δ spectra, where the standard Benjamin–Feir instability is recovered, and to more general spectra. In that context, we present a scheme for the numerical resolution of the Penrose condition and estimate the sharpest possible localization of unstable modes. Keywords: Rogue Waves; Wigner equation; Nonlinear Schrodinger equation; Penrose modes; Penrose conditio

European Association of Urology Guidelines Office Rapid Reaction Group: An Organisation-wide Collaborative Effort to Adapt the European Association of Urology Guidelines Recommendations to the Coronavirus Disease 2019 Era

The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. As a scientific society, the European Association of Urology, via the guidelines, section offices, and the European Urology family of journals, we believe that it is important that we try to support urologists in this difficult situation. We aim to do this by providing tools that can facilitate decision making with the goal to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible, although it is clear that it is not always possible to mitigate them entirely. We hope that these revised recommendations will fill an important urological practice void and assist urologist surgeons across the globe as they do their very best to deal with the crisis of our generation

Robustness and uncertainties in global multivariate wind-wave climate projections

Understanding climate-driven impacts on the multivariate global wind-wave climate is paramount to effective offshore/coastal climate adaptation planning. However, the use of single-method ensembles and variations arising from different methodologies has resulted in unquantified uncertainty amongst existing global wave climate projections. Here, assessing the first coherent, community-driven, multi-method ensemble of global wave climate projections, we demonstrate widespread ocean regions with robust changes in annual mean significant wave height and mean wave period of 5–15% and shifts in mean wave direction of 5–15°, under a high-emission scenario. Approximately 50% of the world’s coastline is at risk from wave climate change, with ~40% revealing robust changes in at least two variables. Furthermore, we find that uncertainty in current projections is dominated by climate model-driven uncertainty, and that single-method modelling studies are unable to capture up to ~50% of the total associated uncertainty

The Vascular Impairment of Cognition Classification Consensus Study

Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. / Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. / Results: VICCCS had a mean of 122 (98–153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. / Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research