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.

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.

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.

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.

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.

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.

Post-Acute Care for Older People Following Injury: A Randomized Controlled Trial.

OBJECTIVES: The study sought to determine whether older people, on discharge from hospital and on referral to a supported discharge team (SDT), will have: (1) reduced length of stay in hospital; (2) reduced risk of hospital readmission; and (3) reduced healthcare costs. DESIGN/INTERVENTION: Randomized controlled trial with follow-up at 4 and 12 months of post-acute home-based rehabilitation team (SDT). Programs were delivered by trained healthcare assistants, up to 4 times a day, 7 days a week, under the guidance of registered nurses, allied health, and geriatricians for up to 6 weeks. PARTICIPANTS/SETTING: A total of 303 older women and 100 older men (mean age 81) in hospital because of injury, were randomized to either SDT (n = 201) or usual care (n = 202). The intervention was operated from Waikato hospital, a regional hospital in New Zealand. METHODS: Days spent in hospital in the year following randomization and healthcare costs were collected from hospital datasets, and functional status assessed using the interRAI Contact Assessment was gathered by health professional research associates. RESULTS: Participants randomized to the SDT spent less time in hospital in the period immediately prior to discharge (mean 20.9 days) in comparison to usual care (mean 26.6 days) and spent less time in hospital in the 12 months following discharge home. Healthcare costs were lower in the SDT group in the 12 months following randomization. CONCLUSIONS/IMPLICATIONS: SDT can provide an important role in reducing hospital length of stay and readmissions of older people following an injury. Almost a million older people (65+ years of age) a year in the US are hospitalized as a consequence of falls-related injuries, most often fractured hip. Hospitals are not always the best location to provide care for older people. SDTs can help with the transition from hospital to home, while reducing hospital length-of-stay.

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.

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.

Using benchmarking to assist the improvement of service quality in home support services for older people-IN TOUCH (Integrated Networks Towards Optimising Understanding of Community Health).

Service providers and funders need ways to work together to improve services. Identifying critical performance variables provides a mechanism by which funders can understand what they are purchasing without getting caught up in restrictive service specifications that restrict the ability of service providers to meet the needs of the clients. An implementation pathway and benchmarking programme called IN TOUCH provided contracted providers of home support and funders with a consistent methodology to follow when developing and implementing new restorative approaches for service delivery. Data from performance measurement was used to triangulate the personal and social worlds of the stakeholders enabling them to develop a shared understanding of what is working and what is not. The initial implementation of IN TOUCH involved five District Health Boards. The recursive dialogue encouraged by the IN TOUCH programme supports better and more sustainable service development because performance management is anchored to agreed data that has meaning to all stakeholders.

Developing and utilising a new funding model for home-care services in New Zealand.

Worldwide increases in the numbers of older people alongside an accompanying international policy incentive to support ageing-in-place have focussed the importance of home-care services as an alternative to institutionalisation. Despite this, funding models that facilitate a responsive, flexible approach are lacking. Casemix provides one solution, but the transition from the well-established hospital system to community has been problematic. This research seeks to develop a Casemix funding solution for home-care services through meaningful client profile groups and supporting pathways. Unique assessments from 3,135 older people were collected from two health board regions in 2012. Of these, 1,009 arose from older people with non-complex needs using the interRAI-Contact Assessment (CA) and 2,126 from the interRAI-Home-Care (HC) from older people with complex needs. Home-care service hours were collected for 3 months following each assessment and the mean weekly hours were calculated. Data were analysed using a decision tree analysis, whereby mean hours of weekly home-care was the dependent variable with responses from the assessment tools, the independent variables. A total of three main groups were developed from the interRAI-CA, each one further classified into "stable" or "flexible." The classification explained 16% of formal home-care service hour variability. Analysis of the interRAI-HC generated 33 clusters, organised through eight disability "sub" groups and five "lead" groups. The groupings explained 24% of formal home-care services hour variance. Adopting a Casemix system within home-care services can facilitate a more appropriate response to the changing needs of older people.

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.

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.

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.

How efficient are New Zealand's District Health Boards at producing life expectancy gains for Maori and Europeans?

OBJECTIVE: Use data envelopment analysis (DEA) to measure the efficiency of New Zealand's District Health Boards (DHBs) at achieving gains in Maori and European life expectancy (LE). METHODS: Using life tables for 2006 and 2013, a two-output DEA model established the production possibility frontier for Maori and European LE gain. Confidence limits were generated from a 10,000 replicate Monte Carlo simulation. RESULTS: Results support the use of LE change as an indicator of DHB efficiency. DHB mean income and education were related to initial LE but not to its rate of change. LE gains were unrelated to either the initial level of life expectancy or to the proportion of Maori in the population. DHB efficiency ranged from 79% to 100%. Efficiency was significantly correlated with DHB financial performance. CONCLUSION: Changes in LE did not depend on the social characteristics of the DHB. The statistically significant association between efficiency and financial performance supports its use as an indicator of managerial effectiveness. Implications for public health: Efficient health systems achieve better population health outcomes. DEA can be used to measure the relative efficiency of sub-national health authorities at achieving health gain and equity outcomes.

Outreach immunisation services in NewZealand: a review of service delivery models.

INTRODUCTION Outreach Immunisation Services (OIS) enable children who have not been immunised on time at general practice to be immunised in the community, thereby improving immunisation coverage and reducing equity gaps. AIM To identify the most effective service delivery models and make recommendations for more effective and cost-efficient OIS delivery in New Zealand. METHODS Data collection and thematic analysis through a detailed review of OIS contracts and service specifications, an online survey and in-depth interviews with stakeholders and providers, and an analysis of cost data was conducted. RESULTS In total, 28 OIS providers completed survey questionnaires, 28 OIS staff were interviewed, and cost effectiveness data were obtained from 11 providers. The surveys and interviews identified key themes around identifying clients with the highest needs, effective engagement strategies, staffing requirements, and service challenges. On average, each OIS referral costs NZ$361 (median NZ$257), and each vaccination event costs NZ$636, ranging from NZ$145 to NZ$2403. Characteristics for two separate models of service delivery were identified based on provider size. CONCLUSION There is considerable range in costs and style of OIS delivery, and efficiencies can be gained. Models need to fit with locality needs and include adequate resourcing, staff with good local knowledge, close relationships with other key child health services and preferably co-location, sustainable funding, and regular service reviews. OIS are part of an effective integrated service that relies on accurate data, positive relationships and a rapid response when children fail to present for vaccination in a timely fashion.

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.