Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer

Funding Information: Acknowledgments: Rui M. Bernardino is supported by Fundacao para a Ciencia e a Tecnologia (2022.13386.BD). Publisher Copyright: © 2023 European Association of UrologyBackground: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions. Objective: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples. Design, setting, and participants: Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study. Outcome measurements and statistical analysis: We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC. Results and limitations: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36–49%) for detection of cribriform morphology and 44.1% (95% CI 36–52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47–58%). Among patients who underwent multiparametric magnetic resonance imaging–guided biopsies, the sensitivity was 54% (95% CI 39–68%) for detection of cribriform morphology and 37% (95% CI 19–58%) for detection of IDC. Conclusions: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed. Patient summary: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.proofepub_ahead_of_prin

Study protocol: Comparison of different risk prediction modelling approaches for COVID-19 related death using the OpenSAFELY platform

On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and individual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19. In order to make informed decisions, both individual and collective, good predictive models are required.   For outcomes related to an infectious disease, the performance of any risk prediction model will depend heavily on the underlying prevalence of infection in the population of interest. Incorporating measures of how this changes over time may result in important improvements in prediction model performance.  This protocol reports details of a planned study to explore the extent to which incorporating time-varying measures of infection burden over time improves the quality of risk prediction models for COVID-19 death in a large population of adult patients in England. To achieve this aim, we will compare the performance of different modelling approaches to risk prediction, including static cohort approaches typically used in chronic disease settings and landmarking approaches incorporating time-varying measures of infection prevalence and policy change, using COVID-19 related deaths data linked to longitudinal primary care electronic health records data within the OpenSAFELY secure analytics platform.</ns4:p

Co-productive agility and four collaborative pathways to sustainability transformations

Co-production, the collaborative weaving of research and practice by diverse societal actors, is argued to play an important role in sustainability transformations. Yet, there is still poor understanding of how to navigate the tensions that emerge in these processes. Through analyzing 32 initiatives worldwide that co-produced knowledge and action to foster sustainable social-ecological relations, we conceptualize ‘co-productive agility’ as an emergent feature vital for turning tensions into transformations. Co-productive agility refers to the willingness and ability of diverse actors to iteratively engage in reflexive dialogues to grow shared ideas and actions that would not have been possible from the outset. It relies on embedding knowledge production within processes of change to constantly recognize, reposition, and navigate tensions and opportunities. Co-productive agility opens up multiple pathways to transformation through: (1) elevating marginalized agendas in ways that maintain their integrity and broaden struggles for justice; (2) questioning dominant agendas by engaging with power in ways that challenge assumptions, (3) navigating conflicting agendas to actively transform interlinked paradigms, practices, and structures; (4) exploring diverse agendas to foster learning and mutual respect for a plurality of perspectives. We explore six process considerations that vary by these four pathways and provide a framework to enable agility in sustainability transformations. We argue that research and practice spend too much time closing down debate over different agendas for change – thereby avoiding, suppressing, or polarizing tensions, and call for more efforts to facilitate better interactions among different agendas

Co-productive agility and four collaborative pathways to sustainability transformations

Co-production, the collaborative weaving of research and practice by diverse societal actors, is argued to play an important role in sustainability transformations. Yet, there is still poor understanding of how to navigate the tensions that emerge in these processes. Through analyzing 32 initiatives worldwide that co-produced knowledge and action to foster sustainable social-ecological relations, we conceptualize ‘co-productive agility’ as an emergent feature vital for turning tensions into transformations. Co-productive agility refers to the willingness and ability of diverse actors to iteratively engage in reflexive dialogues to grow shared ideas and actions that would not have been possible from the outset. It relies on embedding knowledge production within processes of change to constantly recognize, reposition, and navigate tensions and opportunities. Co-productive agility opens up multiple pathways to transformation through: (1) elevating marginalized agendas in ways that maintain their integrity and broaden struggles for justice; (2) questioning dominant agendas by engaging with power in ways that challenge assumptions, (3) navigating conflicting agendas to actively transform interlinked paradigms, practices, and structures; (4) exploring diverse agendas to foster learning and mutual respect for a plurality of perspectives. We explore six process considerations that vary by these four pathways and provide a framework to enable agility in sustainability transformations. We argue that research and practice spend too much time closing down debate over different agendas for change – thereby avoiding, suppressing, or polarizing tensions, and call for more efforts to facilitate better interactions among different agendas

Comparison of methods for predicting COVID-19-related death in the general population using the OpenSAFELY platform.

BACKGROUND: Obtaining accurate estimates of the risk of COVID-19-related death in the general population is challenging in the context of changing levels of circulating infection. METHODS: We propose a modelling approach to predict 28-day COVID-19-related death which explicitly accounts for COVID-19 infection prevalence using a series of sub-studies from new landmark times incorporating time-updating proxy measures of COVID-19 infection prevalence. This was compared with an approach ignoring infection prevalence. The target population was adults registered at a general practice in England in March 2020. The outcome was 28-day COVID-19-related death. Predictors included demographic characteristics and comorbidities. Three proxies of local infection prevalence were used: model-based estimates, rate of COVID-19-related attendances in emergency care, and rate of suspected COVID-19 cases in primary care. We used data within the TPP SystmOne electronic health record system linked to Office for National Statistics mortality data, using the OpenSAFELY platform, working on behalf of NHS England. Prediction models were developed in case-cohort samples with a 100-day follow-up. Validation was undertaken in 28-day cohorts from the target population. We considered predictive performance (discrimination and calibration) in geographical and temporal subsets of data not used in developing the risk prediction models. Simple models were contrasted to models including a full range of predictors. RESULTS: Prediction models were developed on 11,972,947 individuals, of whom 7999 experienced COVID-19-related death. All models discriminated well between individuals who did and did not experience the outcome, including simple models adjusting only for basic demographics and number of comorbidities: C-statistics 0.92-0.94. However, absolute risk estimates were substantially miscalibrated when infection prevalence was not explicitly modelled. CONCLUSIONS: Our proposed models allow absolute risk estimation in the context of changing infection prevalence but predictive performance is sensitive to the proxy for infection prevalence. Simple models can provide excellent discrimination and may simplify implementation of risk prediction tools

Exploring and expanding transdisciplinary research for sustainable and just natural resource management.

Transdisciplinarity is gaining acceptance in sustainability science research as an approach to work across disparate types of knowledge and practices in order to tackle complex social-ecological problems. On paper, transdisciplinarity appears to be substantially helpful, but in practice, participants may remain voiceless and disadvantaged. In this paper, we retrospectively investigate four case studies using recent design principles for transdisciplinary research, to explore a deeper understanding of the practical successes and failures of transdisciplinary research engagement. We show that the transdisciplinary way of working is time consuming, challenging, and insists that researchers and participants contribute reflexively. Careful attention to research design and methodology is central. The acceptance that complexity renders knowledge provisional, and complete honesty about the purpose of the research are critical to building relationships between researchers and participants. Gaining an understanding of the values people hold influences the research process and the possible outcomes toward sustainable and just natural resource management. We suggest that in order to enable sustainable and just natural resource management, transdisciplinary research should include values and ethics in the design, implementation, and reporting of projects

Adolescent use of flavored non-tobacco oral nicotine products.

BACKGROUND AND OBJECTIVES: Flavored non-tobacco oral nicotine products (eg, nicotine pouches and nontherapeutic nicotine gum, lozenges, tablets, gummies), are increasingly marketed in the United States. Prevalence of non-tobacco oral nicotine product use among adolescents is unknown. METHODS: We calculated prevalence of ever and past 6-month use of nicotine pouches, other non-tobacco oral nicotine products (ie, gum, lozenges, tablets, and/or gummies), e-cigarettes, cigarettes, hookah or waterpipe, cigars, cigarillos, and snus among high school students in Southern California between September and December 2021. Generalized linear mixed models tested associations of sociodemographic factors and tobacco-product use with use of any non-tobacco oral nicotine product. RESULTS: Among the sample (n = 3516), prevalence was highest for e-cigarettes (ever: 9.6%, past 6-month: 5.5%), followed by non-tobacco oral nicotine products (ever: 3.4%, past 6-month: 1.7%), and <1% for other products. Ever users of combustible tobacco and ever users of noncombustible tobacco had higher odds of ever using non-tobacco oral nicotine products, compared to never users of combustible and noncombustible tobacco. Use of any non-tobacco oral nicotine product was greater for Hispanic (versus all other races/ethnicities except Asian), sexual minority (versus heterosexual), gender minority (versus male), and female (versus male) participants. CONCLUSIONS: Non-tobacco oral nicotine products were the second most prevalent nicotine product used by adolescents. They were disproportionately used by certain racial or ethnic, sexual, or gender minority groups, and those with a history of nicotine use. Adolescent non-tobacco oral nicotine product use surveillance should be a public health priority