Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014)

Men's experiences of radiotherapy treatment for localized prostate cancer and its long-term treatment side effects: a longitudinal qualitative study.

PURPOSE: To investigate men's experiences of receiving external-beam radiotherapy (EBRT) with neoadjuvant Androgen Deprivation Therapy (ADT) for localized prostate cancer (LPCa) in the ProtecT trial. METHODS: A longitudinal qualitative interview study was embedded in the ProtecT RCT. Sixteen men with clinically LPCa who underwent EBRT in ProtecT were purposively sampled to include a range of socio-demographic and clinical characteristics. They participated in serial in-depth qualitative interviews for up to 8 years post-treatment, exploring experiences of treatment and its side effects over time. RESULTS: Men experienced bowel, sexual, and urinary side effects, mostly in the short term but some persisted and were bothersome. Most men downplayed the impacts, voicing expectations of age-related decline, and normalizing these changes. There was some reticence to seek help, with men prioritizing their relationships and overall health and well-being over returning to pretreatment levels of function. Some unmet needs with regard to information about treatment schedules and side effects were reported, particularly among men with continuing functional symptoms. CONCLUSIONS: These findings reinforce the importance of providing universal clear, concise, and timely information and supportive resources in the short term, and more targeted and detailed information and care in the longer term to maintain and improve treatment experiences for men undergoing EBRT

Men’s experiences of radiotherapy treatment for localized prostate cancer and its long‑term treatment side effects:a longitudinal qualitative study

Purpose To investigate men’s experiences of receiving external-beam radiotherapy (EBRT) with neoadjuvant Androgen Deprivation Therapy (ADT) for localized prostate cancer (LPCa) in the ProtecT trial. Methods A longitudinal qualitative interview study was embedded in the ProtecT RCT. Sixteen men with clinically LPCa who underwent EBRT in ProtecT were purposively sampled to include a range of socio-demographic and clinical characteristics. They participated in serial in-depth qualitative interviews for up to 8 years post-treatment, exploring experiences of treatment and its side effects over time. Results Men experienced bowel, sexual, and urinary side effects, mostly in the short term but some persisted and were bothersome. Most men downplayed the impacts, voicing expectations of age-related decline, and normalizing these changes. There was some reticence to seek help, with men prioritizing their relationships and overall health and well-being over returning to pretreatment levels of function. Some unmet needs with regard to information about treatment schedules and side effects were reported, particularly among men with continuing functional symptoms. Conclusions These findings reinforce the importance of providing universal clear, concise, and timely information and supportive resources in the short term, and more targeted and detailed information and care in the longer term to maintain and improve treatment experiences for men undergoing EBRT

Factors associated with trial recruitment, preferences, and treatments received were elucidated in a comprehensive cohort study

Objectives:&nbsp;Recruitment to pragmatic trials is often difficult, and little is known about factors associated with key participation and treatment decisions. These were explored in the Prostate cancer testing and Treatment (ProtecT) study. Study Design and Setting:&nbsp;Baseline sociodemographic, patient-reported outcome, clinical history, and prostate cancer biopsy data were collected for all patients eligible to take part in the ProtecT trial, in a comprehensive cohort design. Men who rejected randomization specified a preferred option and were followed up identically to the randomized cohort. Factors associated with participation decisions, patient preferences, and reasons for changing treatment were explored. Results:&nbsp;Of 2,664 men with clinically localized prostate cancer, 997 (37%) rejected randomization. Their treatment preferences and subsequent treatment choices/changes in both randomized and treatment choice cohorts were strongly associated with prostate cancer risk features: toward active monitoring for low-risk disease and toward radical options with higher risk prostate cancer. Among many factors measured, only a small number of weak associations were found for occupation groups and some patient symptoms. Similar percentages changed from the random allocation and initially stated preference. Conclusion:&nbsp;The comprehensive cohort design provided new insights into trial recruitment and participation decisions. Opportunities to improve recruitment by supporting recruiters with equipoise and patient preferences were identified.</p

Interaction of Copper-Amine With Southern Pine: Retention and Migration

The retention and leachability of copper in copper-amine (Cu-EA)-treated southern pine (SP) are influenced by the formulation and the composition of copper-amine treating solutions. The sources of copper used, Cu(OH)2, CuCO3, CuSO4, and Cu(NO3)2, in the copper-amine complex formulation affect the leachability of copper. Data show that copper-amine from CuSO4- and Cu(NO3)2-treated wood has less copper loss during laboratory water leaching than that from Cu(OH)2- and CuCO3-treated wood. Increasing the amine-to-copper molar ratio increases the copper retention by wood, but reduces the leach resistance of copper. The nature of amine ligands, such as monoethanolamine (primary amine), 2-methylamino-ethanol (secondary amine), and N, N-dimethyl-ethanolamine (tertiary amine), has some effect on copper retention and copper leaching. As the molecular weight of amine ligands increases, copper loss during leaching decreases

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial

$\textit{Background:}$ Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. $\textit{Objective:}$ To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. $\textit{Design, setting, and participants:}$ Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. $\textit{Outcome measurements and statistical analysis:}$ PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox’s proportional hazards regression. $\textit{Results and limitations:}$ Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0 = 5, M1 = 32) and 305 had locally advanced disease (62%). The median PSA was 17 $\mu$g/l. Treatments included radical prostatectomy (RP; $n$ = 54; 11%), radiotherapy (RT; $n$ = 245; 50%), androgen deprivation therapy (ADT; $n$ = 122; 25%), other treatments ($n$ = 11; 2%), and unknown ($n$ = 60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38–0.83; $p$ = 0.0037), but mortality was similar in those treated radically. The non-randomised design is a limitation. $\textit{Conclusions:}$ Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. $\textit{Patient summary:}$ Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.The ProtecT trial is funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment Programme (projects 96/20/06, 96/20/99) with the University of Oxford as sponsor (www.nets.nihr.ac.uk/projects/hta/962099). The sponsor played a role in the design and conduct of the study. Jenny L. Donovan is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West, hosted by University Hospitals Bristol NHS Foundation Trust. Freddie C. Hamdy is supported by the Oxford NIHR Biomedical Research Centre Surgical Innovation and Evaluation Theme, and the Cancer Research UK Oxford Centre

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Informed consent in randomised controlled trials: development and preliminary evaluation of a measure of participatory and informed consent (PIC)

Background Informed consent (IC) is an ethical and legal prerequisite for trial participation, yet current approaches evaluating participant understanding for IC during recruitment lack consistency. No validated measure has been identified that evaluates participant understanding for IC based on their contributions during consent interactions. This paper outlines the development and formative evaluation of the Participatory and Informed Consent (PIC) measure for application to recorded recruitment appointments. The PIC allows the evaluation of recruiter information provision and evidence of participant understanding. Methods Published guidelines for IC were reviewed to identify potential items for inclusion. Seventeen purposively sampled trial recruitment appointments from three diverse trials were reviewed to identify the presence of items relevant to IC. A developmental version of the measure (DevPICv1) was drafted and applied to six further recruitment appointments from three further diverse trials to evaluate feasibility, validity, stability and inter-rater reliability. Findings guided revision of the measure (DevPICv2) which was applied to six further recruitment appointments as above. Results DevPICv1 assessed recruiter information provision (detail and clarity assessed separately) and participant talk (detail and understanding assessed separately) over 20 parameters (or 23 parameters for three-arm trials). Initial application of the measure to six diverse recruitment appointments demonstrated promising stability and inter-rater reliability but a need to simplify the measure to shorten time for completion. The revised measure (DevPICv2) combined assessment of detail and clarity of recruiter information and detail and evidence of participant understanding into two single scales for application to 22 parameters or 25 parameters for three-arm trials. Application of DevPICv2 to six further diverse recruitment appointments showed considerable improvements in feasibility (e.g. time to complete) with good levels of stability (i.e. test-retest reliability) and inter-rater reliability maintained. Conclusions The DevPICv2 provides a measure for application to trial recruitment appointments to evaluate quality of recruiter information provision and evidence of patient understanding and participation during IC discussions. Initial evaluation shows promising feasibility, validity, reliability and ability to discriminate across a range of recruiter practice and evidence of participant understanding. More validation work is needed in new clinical trials to evaluate and refine the measure further

”Medialle pitäis kertoa positiivisiakin asioita eikä vaan niitä kamalia ja huonoja” : lastensuojeluun liittyviä mielikuvia, niiden taustaa ja tulevaisuutta

Tämän opinnäytetyön tarkoituksena oli selvittää ihmisten mielikuvia ja tietämystä lastensuojelusta sekä tietämystä viime vuonna voimaan tulleesta uudesta sosiaalihuoltolaista. Lisäksi tarkoituksena oli kartoittaa mistä lähteestä saatuun tietoon heidän mielikuvansa lastensuojelusta heidän omasta mielestään perustuvat sekä miten lastensuojelun tulisi toimia, jotta se heidän mielikuvissaan toimisi kaikilta osin hyvin. Työssä haluttiin vielä selvittää, mitä ajatuksia sosiaalihuoltolain muutokset ihmisissä herättävät sekä miten heidän mielestään lastensuojelusta ja lakimuutoksista tiedottaminen tulisi hoitaa. Tutkimusotteena käytettiin laadullista tutkimusta. Tutkimusaineisto kerättiin haastattelemalla ihmisiä Tampereen keskustassa ja lähialueilla huhti-toukokuussa 2016. Haastatteluita tehtiin kaksikymmentä, joista saatu aineisto analysoitiin aineistolähtöisen sisällönanalyysin keinoin. Opinnäytetyön teoreettinen viitekehys käsittelee lastensuojelua sekä mielikuvia. Opinnäytetyön tulosten mukaan sellaiset ihmiset, joilla ei ole lastensuojelusta henkilökohtaista kokemusta, eivät tiedä alalla tehtävästä käytännön työstä tai lakimuutoksesta paljoakaan. Mielikuvat lastensuojelusta ovat rakentuneet hyvin vahvasti median kautta tai muista arjen tietolähteistä, kuten muiden ihmisten puheista, saadun informaation perusteella. Faktatietoa lastensuojelun toiminnasta tai edes sen tehtävistä yhteiskunnassa ei ihmisillä juurikaan ole. Tulosten mukaan lastensuojelutyöhön kaivataan lisää avoimuutta ja läpinäkyvyyttä sekä positiivista julkisuutta. Mielikuvat lastensuojelusta olisivat paremmat, mikäli työssä olisi enemmän ja tehokkaammin kohdistettuja resursseja, siinä panostettaisiin enemmän ennaltaehkäisevään työhön ja apua olisi helpommin ja nopeammin saatavilla. Lakimuutokset herättivät ihmisissä positiivisia ajatuksia, ja he kokivat, että ne vievät työtä oikeaan suuntaan. Lastensuojeluun liittyvistä asioista tiedottamisessa haastatellut toivoivat käytettävän monipuolisesti eri medioita sekä muun muassa kouluja ja neuvoloita. Johtopäätöksenä voidaan todeta, että median rooli lastensuojeluun liittyvän tiedon jakamisessa ja siihen liittyvien mielikuvien parantamisessa on keskeinen. Sosiaalihuoltolain muutokset ovat viemässä työn painopistettä oikeaan suuntaan, ja tämän positiivisen muutoksen tukemisessa tarvitaan paitsi riittäviä resursseja, myös panostusta tiedottamiseen sekä avoimeen ja positiiviseen julkisuuteen työntekijätahon puolelta.The purpose of was to collect data on people's knowledge and mental image regarding Child welfare services, and their knowledge and opinion about changes in Social welfare law that came into effect last year. Also the purpose was to find out from what source they have gotten the information their mental image is founded on, how Child welfare services should change to make people's mental image better, and how municipalities should inform public about these matters. The study was qualitative in nature and the data were collected interviewing people in Tampere center and nearby areas. The data were content analysed. The results show that people not in contact with Child welfare services in their everyday life do not know many facts about their function, nore about the changes in Social welfare law. Mental images people have are founded on information from the media or ordinary life sources like other people's stories. Child welfare services should be more transparent, have more positive visibility in media, have better resources and invest more to preventive work. Interviewees found that the changes in Social welfare law take this line of work to the right direction. As sources of information they thought that different medias, schools and child health centers would be most efficient. The conclusion was that media has a central role in sharing information and improving the mental image concerning Child welfare. Changes in the Social welfare law are taking the focus of Child welfare services to the right direction. Supporting this positive change requires not only sufficient resources but also investment from workers in providing more information and taking part in positive publicity