An induced thymic epithelial cell-based high throughput screen for thymus extracellular matrix mimetics.

Thymic epithelial cells (TECs) are key effectors of the thymic stroma and are critically required for T-cell development. TECs comprise a diverse set of related but functionally distinct cell types that are scarce and difficult to isolate and handle. This has precluded TEC-based screening assays. We previously described induced thymic epithelial cells (iTECs), an artificial cell type produced in vitro by direct reprogramming, raising the possibility that iTECs might provide the basis for functional screens related to TEC biology. Here, we present an iTEC-based three-stage medium/high-throughput in vitro assay for synthetic polymer mimics of thymic extracellular matrix (ECM). Using this assay, we identified, from a complex library, four polymers that bind iTEC as well as or better than gelatin but do not bind mesenchymal cells. We show that these four polymers also bind and maintain native mouse fetal TECs and native human fetal TECs. Finally, we show that the selected polymers do not interfere with iTEC function or T-cell development. Collectively, our data establish that iTECs can be used to screen for TEC-relevant compounds in at least some medium/high-throughput assays and identify synthetic polymer ECM mimics that can replace gelatin or ECM components in TEC culture protocols.

Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development.

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). However, the mechanisms controlling cTEC and mTEC production from the common TEPC are not understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPCs at the expense of cTEC differentiation. Finally, we uncover a cross-regulatory relationship between NOTCH and FOXN1, a master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development, and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo.

Performance measurement of nonhomogeneous Hong Kong hospitals using directional distance functions.

Cook et al. (Oper Res 61(3):666-676, 2013) propose a DEA-based model for the performance evaluation of non-homogeneous decision making units (DMUs) based on constant returns to scale (CRS), extended by Li et al. (Health Care Manag Sci 22(2):215-228, 2019) to variable returns to scale (VRS). This paper locates these models into more general DDF models to deal with nonhomogeneous DMUs and applies these to Hong Kong hospitals. The production process of each hospital is divided into subunits which have the same inputs and outputs and hospital performance is measured using the subunits. The paper provides CRS and VRS versions of DDF models and compares them with Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019). A kernel-based method is used to estimate the distributions as well as a DEA-based efficiency analysis adapted by Simar and Zelenyuk to test the distributions. Both DDF CRS and VRS versions produce results similar to Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019) respectively. However, the statistical tests find differences for the different technologies assumed as would be expected. For hospital managers, the more generalised DDF models expand their range of options in terms of directional improvements and priorities as well as dealing with non-homogeneity.

Measuring work complexity for acute care services.

Case weights capture the resource cost by diagnosis-related group (DRG) but may not fully reflect the complexity of the clinical services provided. This study describes the use of a work complexity index (WCI), for assessing acute care services focusing on those provided by physicians in healthcare systems. The services are classified using relative value units (RVUs) and their point value assigned using the resource-based relative value scale. 57,559 acute inpatients from a tertiary hospital were first classified into diagnosis-related groups, which together with the relative value units assigned to services were then used to calculate a work complexity index for 38 departments. A case mix index (CMI) was also compiled as a conventional measure of complexity which had a correlation of 0.676 (p < 0.001) with the WCI. The correlation between the WCI and the RVUs representing the weighted volume of physician activities was 0.342 (p = 0.036). The WCI represents a more output or activity focused measure of complexity whereas the CMI is more patient focused and thus provides better insights into Departments' productivity. Although this paper focuses on physicians, the WCI can be easily extended to include other clinical services.

A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency.

Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.

Supported Discharge Teams for older people in hospital acute care: a randomised controlled trial.

Background: Supported Discharge Teams aim to help with the transition from hospital to home, whilst reducing hospital length-of-stay. Despite their obvious attraction, the evidence remains mixed, ranging from strong support for disease-specific interventions to less favourable results for generic services. Objective: To determine whether older people referred to a Supported Discharge Team have: (i) reduced length-of-stay in hospital; (ii) reduced risk of hospital readmission; and (iii) reduced healthcare costs. Methods: Randomised controlled trial with follow-up to 6 months; 103 older women and 80 men (n = 183) (mean age 79), in hospital, were randomised to receive either Supported Discharge Team or usual care. Home-based rehabilitation was delivered by trained Health Care Assistants up to four times a day, 7 days a week, under the guidance of registered nurses, allied health and geriatricians for up to 6 weeks. Results: Participants randomised to the Supported Discharge Team spent less time in hospital during the index admission (mean 15.7 days) in comparison to usual care (mean 21.6 days) (mean difference 5.9: 95% CI 0.6, 11.3 days: P = 0.03) and spent less time in hospital in the 6 months following discharge home. Supported discharge group costs were calculated at mean NZ$10,836 (SD NZ$12,087) compared to NZ$16,943 (SD NZ$22,303) in usual care. Conclusion: A Supported Discharge Team can provide an effective means of discharging older people home early from hospital and can make a cost-effective contribution to managing increasing demand for hospital beds.

Using Robots at Home to Support Patients With Chronic Obstructive Pulmonary Disease: Pilot Randomized Controlled Trial.

BACKGROUND: Socially assistive robots are being developed for patients to help manage chronic health conditions such as chronic obstructive pulmonary disease (COPD). Adherence to medication and availability of rehabilitation are suboptimal in this patient group, which increases the risk of hospitalization. OBJECTIVE: This pilot study aimed to investigate the effectiveness of a robot delivering telehealth care to increase adherence to medication and home rehabilitation, improve quality of life, and reduce hospital readmission compared with a standard care control group. METHODS: At discharge from hospital for a COPD admission, 60 patients were randomized to receive a robot at home for 4 months or to a control group. Number of hospitalization days for respiratory admissions over the 4-month study period was the primary outcome. Medication adherence, frequency of rehabilitation exercise, and quality of life were also assessed. Implementation interviews as well as benefit-cost analysis were conducted. RESULTS: Intention-to-treat and per protocol analyses showed no significant differences in the number of respiratory-related hospitalizations between groups. The intervention group was more adherent to their long-acting inhalers (mean number of prescribed puffs taken per day=48.5%) than the control group (mean 29.5%, P=.03, d=0.68) assessed via electronic recording. Self-reported adherence was also higher in the intervention group after controlling for covariates (P=.04). The intervention group increased their rehabilitation exercise frequency compared with the control group (mean difference -4.53, 95% CI -7.16 to -1.92). There were no significant differences in quality of life. Of the 25 patients who had the robot, 19 had favorable attitudes. CONCLUSIONS: This pilot study suggests that a homecare robot can improve adherence to medication and increase exercise. Further research is needed with a larger sample size to further investigate effects on hospitalizations after improvements are made to the robots. The robots could be especially useful for patients struggling with adherence. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000259549; http://www.anzctr.org.au (Archived by WebCite at  http://www.webcitation.org/6whIjptLS).

Impact of an assertive community treatment model of care on the treatment of prisoners with a serious mental illness.

OBJECTIVES: This study aims to describe the impact of a mental health assertive community treatment prison model of care (PMOC) on improving the ability to identify prisoner needs, provide interventions and monitor their efficacy. METHODS: We carried out a file review across five prisons of referrals in the year before the implementation of the PMOC in 2010 ( n = 423) compared with referrals in the year after ( n = 477). RESULTS: Some improvements in the identification of needs and providing interventions were detected. There was increased use of medication management and clinically significant improvement in addressing engagement with families. Monthly multi-disciplinary team face-to-face contact improved. CONCLUSIONS: Meeting the needs of mentally ill prisoners is challenged by the complexity of the custodial environment. Improvements made resulted from changing the model of care, rather than adding new resources.

The cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer.

BACKGROUND: Radical prostatectomy is the most common treatment for localised prostate cancer in New Zealand. Active surveillance was introduced to prevent overtreatment and reduce costs while preserving the option of radical prostatectomy. This study aims to evaluate the cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy. METHODS: Markov models were constructed to estimate the life-time cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer patients aged 45-70 years, using national datasets in New Zealand and published studies including the SPCG-4 study. This study was from the perspective of the Ministry of Health in New Zealand. RESULTS: Radical prostatectomy is less costly than active surveillance in men aged 45-55 years with low risk localised prostate cancer, but more costly for men aged 60-70 years. Scenario analyses demonstrated significant uncertainty as to the most cost-effective option in all age groups because of the unavailability of good quality of life data for men under active surveillance. Uncertainties around the likelihood of having radical prostatectomy when managed with active surveillance also affect the cost-effectiveness of active surveillance against radical prostatectomy. CONCLUSIONS: Active surveillance is less likely to be cost-effective compared to radical prostatectomy for younger men diagnosed with low risk localised prostate cancer. The cost-effectiveness of active surveillance compared to radical prostatectomy is critically dependent on the 'trigger' for radical prostatectomy and the quality of life in men on active surveillance. Research on the latter would be beneficial.

Considerations for using data envelopment analysis for the assessment of radiotherapy treatment plan quality.

Purpose The operations research method of data envelopment analysis (DEA) shows promise for assessing radiotherapy treatment plan quality. The purpose of this paper is to consider the technical requirements for using DEA for plan assessment. Design/methodology/approach In total, 41 prostate treatment plans were retrospectively analysed using the DEA method. The authors investigate the impact of DEA weight restrictions with reference to the ability to differentiate plan performance at a level of clinical significance. Patient geometry influences plan quality and the authors compare differing approaches for managing patient geometry within the DEA method. Findings The input-oriented DEA method is the method of choice when performing plan analysis using the key undesirable plan metrics as the DEA inputs. When considering multiple inputs, it is necessary to constrain the DEA input weights in order to identify potential plan improvements at a level of clinical significance. All tested approaches for the consideration of patient geometry yielded consistent results. Research limitations/implications This work is based on prostate plans and individual recommendations would therefore need to be validated for other treatment sites. Notwithstanding, the method that requires both optimised DEA weights according to clinical significance and appropriate accounting for patient geometric factors is universally applicable. Practical implications DEA can potentially be used during treatment plan development to guide the planning process or alternatively used retrospectively for treatment plan quality audit. Social implications DEA is independent of the planning system platform and therefore has the potential to be used for multi-institutional quality audit. Originality/value To the authors' knowledge, this is the first published examination of the optimal approach in the use of DEA for radiotherapy treatment plan assessment.

From positive screen to engagement in treatment: a preliminary study of the impact of a new model of care for prisoners with serious mental illness.

BACKGROUND: The high prevalence of serious mental illness (SMI) in prisons remains a challenge for mental health services. Many prisoners with SMI do not receive care. Screening tools have been developed but better detection has not translated to higher rates of treatment. In New Zealand a Prison Model of Care (PMOC) was developed by forensic mental health and correctional services to address this challenge. The PMOC broadened triggers for referrals to mental health teams. Referrals were triaged by mental health nurses leading to multidisciplinary team assessment within specified timeframes. This pathway for screening, referral and assessment was introduced within existing resources. METHOD: The PMOC was implemented across four prisons. An AB research design was used to explore the extent to which mentally ill prisoners were referred to and accepted by prison in-reach mental health teams and to determine the proportion of prison population receiving specialist mental health care. RESULTS: The number of prisoners in the study in the year before the PMOC (n = 9,349) was similar to the year after (n = 19,421). 24.6 % of prisoners were screened as per the PMOC in the post period. Referrals increased from 491 to 734 in the post period (Z = -7.23, p < 0.0001). A greater number of triage assessments occurred after the introduction of the PMOC (pre = 458; post = 613, Z = 4.74, p < 0.0001) leading to a significant increase in the numbers accepted onto in-reach caseloads (pre = 338; post = 426, Z = 3.16, p < 0.01). Numbers of triage assessments completed within specified time frames showed no statistically significant difference before or after implementation. The proportion of prison population on in-reach caseloads increased from 5.6 % in the pre period to 7.0 % in the year post implementation while diagnostic patterns did not change, indicating more prisoners with SMI were identified and engaged in treatment. CONCLUSIONS: The PMOC led to increased prisoner numbers across screening, referral, treatment and engagement. Gains were achieved without extra resources by consistent processes and improved clarity of professional roles and tasks. The PMOC described a more effective pathway to specialist care for people with SMI entering prison.

Economic evaluation of prostate cancer screening: a systematic review.

This review, based on published papers, aims to describe the costs of prostate cancer screening and to examine whether prostate cancer screening is cost effective. The estimated cost per cancer detected ranged from €1299 in The Netherlands to US$44,355 in the USA. The estimated cost per life-year saved ranged from US$3000 to US$729,000, while the cost per quality-adjusted life year (QALY) was AU$291,817 and Can$371,100. The most appropriate data for economic evaluation of prostate cancer screening should be the cost per QALY gained. The estimated costs per QALY gained by prostate cancer screening were significantly higher than the cost-effectiveness threshold, suggesting that even when based on favorable randomized controlled trials in younger age groups, prostate cancer screening is still not cost effective.

A prison mental health in-reach model informed by assertive community treatment principles: evaluation of its impact on planning during the pre-release period, community mental health service engagement and reoffending.

BACKGROUND: It is well recognised that prisoners with serious mental illness (SMI) are at high risk of poor outcomes on return to the community. Early engagement with mental health services and other community agencies could provide the substrate for reducing risk. AIM: To evaluate the impact of implementing an assertive community treatment informed prison in-reach model of care (PMOC) on post-release engagement with community mental health services and on reoffending rates. METHODS: One hundred and eighty prisoners with SMI released from four prisons in the year before implementation of the PMOC were compared with 170 such prisoners released the year after its implementation. RESULTS: The assertive prison model of care was associated with more pre-release contacts with community mental health services and contacts with some social care agencies in some prisons. There were significantly more post-release community mental health service engagements after implementation of this model (Z = -2.388, p = 0.02). There was a trend towards reduction in reoffending rates after release from some of the prisons (Z =1.82, p = 0.07). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Assertive community treatment applied to prisoners with mental health problems was superior to 'treatment as usual', but more work is needed to ensure that agencies will engage prisoners in pre-release care. The fact that the model showed some benefits in the absence of any increase in resources suggests that it may be the model per se that is effective.

The costs of identifying undiagnosed prostate cancer in asymptomatic men in New Zealand general practice.

BACKGROUND: Screening for prostate cancer (PCa) using the prostate-specific antigen (PSA) test is widespread in New Zealand. Aim. This study estimates the costs of identifying a new case of PCa by screening asymptomatic men. METHODS: Men aged 40+, who had PSA tests in 31 general practices in the Midland Cancer Network region during 2010, were identified. Asymptomatic men without a history of PCa were eligible for this study. A decision tree was constructed to estimate the screening costs. We assumed GPs spent 3 minutes of the initial consultation on informed consent of PCa screening. RESULTS: About 70.7% of the estimated costs were incurred in general practice. The screening costs per cancer detected were NZ$10 777 (€5820; £4817). The estimated costs for men aged 60-69 were NZ$6268 compared to NZ$24 290 for men aged 40-49, NZ$30 022 for 50-59 and NZ$10 957 for those aged 70+. The costs for Maori were NZ$7685 compared to NZ$11 272 for non-Maori. The costs for men without PSA testing history in 2007-09 were NZ$8887 compared to NZ$13 870 if the men had PSA tests in 2007-09. If we assumed a PSA test involved a full 15-minute general practice consultation, the estimated costs increased to NZ$26 877 per PCa identified. CONCLUSIONS: Screening of asymptomatic men for PCa is widely practiced. Most of the costs of screening were incurred in general practice. Calls for men to receive increased information on the harms and benefits of screening will substantially increase the costs. The current costs could be reduced by better targeting of screening.

A randomized controlled trial to determine the effect of a model of restorative home care on physical function and social support among older people.

OBJECTIVE: To determine the impact of a restorative model of home care on social support and physical function among community-dwelling older people. DESIGN: Cluster-randomized controlled trial. SETTING: Home care in an urban area. PARTICIPANTS: Participants (N=205) were randomly assigned to an intervention group (n=108; mean age, 79.1y; 71.3% women; 81.5% New Zealand European [NZE]; 50.8% residing in areas of the highest levels of social deprivation) or a usual care group (n=97; mean age, 76.9y; 60.8% women; 73.2% NZE; 53.5% in the highest levels of social deprivation). INTERVENTION: Participants randomly assigned to the intervention group completed a goal facilitation tool with a needs assessor to determine their needs and to establish the aims for the episode of care. Services were structured according to the principles of restorative home care (independence focused with individually tailored activity programs). Usual care participants received a standard needs assessment that informed the delivery of home care services. MAIN OUTCOME MEASURES: Short Physical Performance Battery (SPPB), Dukes Social Support Index (DSSI). RESULTS: There was greater change over time in physical function (measured by SPPB: F=8.30, P=.003) but no associated increase in social support (as determined by DSSI: F=2.58, P=.09). CONCLUSIONS: Significant improvements in physical function were observed after a period of restorative home care services. The absence of an associated change in social support may have been the result of a combination of factors, including the threshold of physical function required for community ambulation, the low rate of allied health service provision, and the time required to reestablish social ties. The findings contribute to a greater understanding of factors necessary to refocus home-based services to emphasize improvements in physical function and independence.

Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis.

During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population as mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in the understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells.

Goal setting as a feature of homecare services for older people: does it make a difference?

INTRODUCTION: Health services delivered in an older person's home are often implemented at a critical juncture in an individual's functional status. Although homecare has potential to improve this situation, it often focuses on treating disease and 'taking care' of the patient rather than promoting independence. The aim of restorative homecare is to change the philosophy from one where delivery of care may create dependency to provision of care which maximises independence, self-esteem, self-image and quality of life, and reduces the care required. AIMS: To assess impact of a designated goal facilitation tool on health-related quality of life (HRQoL), social support and physical function among community-dwelling older people referred for homecare. METHODS: A total of 205 participants [mean age 79.1 years, 71.3% female (intervention group) and 76.9 years with 60.8% female (control group)] were cluster randomised to an intervention or control assessor. The intervention arm involved participants completing a goal facilitation tool with assessors. This established rehabilitation aims. Control participants received a standard needs assessment. Clients from both groups were then referred to a homecare organisation for service delivery. RESULTS: There was greater change over time in HRQoL [measured by Short Form 36 Survey (SF-36)] in the intervention group (P = 0.0001). There was a marked variation across homecare providers in types of services provided (P < 0.001). Identification of a goal did not predict completion of a formalised review of participants' needs by the homecare organisation. CONCLUSIONS: Use of a goal facilitation tool in assessment of an older person's needs on referral for homecare leads to significant improvements in HRQoL. This may be through a higher proportion of individualised activities tailored to a successful identification of the person's goals. The findings contribute to greater understanding of factors necessary to implement improvements in homecare services for older people.

Efficacy of acute care pathways for older patients: a systematic review and meta-analysis.

Meeting the needs of acute geriatric patients is often challenging, and although evidence shows that older patients need tailored care, it is still unclear which interventions are most appropriate. The objective of this study is to systematically evaluate the hospital-wide acute geriatric models compared with conventional pathways. The design of the study includes hospital-wide geriatric-specific models characterized by components including patient-centered care, frequent medical review, early rehabilitation, early discharge planning, prepared environment, and follow-up after discharge. Primary and secondary outcomes were considered, including functional decline, activities of daily living (ADL), length-of-stay (LoS), discharge destination, mortality, costs, and readmission. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 20 studies reporting on 15 trials and acutely admitted patients with an average age of 79, complex conditions and comorbidities to acute geriatric-specific pathways (N = 13,595) were included. Geriatric-specific models were associated with lower costs (weighted mean difference, WMD = - $174.98, 95% CI = -$332.14 to - $17.82; P = 0.03), and shorter LoS (WMD = - 1.11, 95% CI = - 1.39 to - 0.83; P < 0.001). No differences were found in functional decline, ADL, mortality, case fatalities, discharge destination, or readmissions. Geriatric-specific models are valuable for improving patient and system-level outcomes. Although several interventions had positive results, further research is recommended to study hospital-wide geriatric-specific models. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00743-w.

Multi-parametric magnetic resonance imaging to rule-in and rule-out clinically important prostate cancer in men at risk: a cohort study.

OBJECTIVES: Overdiagnosis is arguably the greatest challenge in the management of men with prostate cancer. Multi-parametric (mp)-MRI prior to prostate biopsy may have a role in ruling-in and ruling-out clinically significant disease. PATIENTS AND METHODS: 114 consecutive men at risk of prostate cancer with previous biopsy underwent mp-MRI prior to transrectal ultrasound (TRUS)-guided biopsies. Standard systematic biopsies were carried out with targeting to suspicious areas. RESULTS: 59.6% had cancer detected by TRUS-guided biopsy. Mean age was 63.6 years (SD 9.0). If men had not been biopsied because of a negative mp-MRI, 21% (24/114) with no cancer and 5% (6/114) with clinically insignificant cancer could have avoided a biopsy. However, 4% (4/114) would have been advised to defer a biopsy that demonstrated the presence of clinically significant cancer. CONCLUSION: mp-MRI may have a role in ruling-in and ruling-out clinically significant prostate cancer in men at risk prior to biopsy.