Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials.

BACKGROUND: Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours. METHODS: The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591. FINDINGS: We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55-85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9-11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (pinteraction=0·0019), higher volume of metastases (pinteraction=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (pinteraction=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (-1%, 95% CI -15 to 12, for progression-free survival; 0%, -10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival). INTERPRETATION: The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes. FUNDING: UK Medical Research Council and Prostate Cancer UK.

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

BACKGROUND: Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS: These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS: Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION: Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476).

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50-0.71; P = 0.31 × 10-9 ) favoured SOC + AAP, with 5-years survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0.55; 95% CI: 0.41-0.76) and high-risk (HR = 0.54; 95% CI: 0.43-0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.

BACKGROUND: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). METHODS AND FINDINGS: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. CONCLUSIONS: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

Psychosocial aspects and support networks associated with disability in two longevous populations in Brazil: a cross-sectional study.

BACKGROUND: Among the oldest old, aged 80 years and over, the prevalence of disability is higher than in other age groups and can be considered a predictor of mortality. OBJECTIVE: To evaluate how psychosocial aspects and support networks influence the disability of these oldest-old individuals, performing a comparison between two longevous populations, one living in one of the poorest regions of Brazil, in the backlands of Paraíba, and another living in one of the largest urban centres in Latin America. METHOD: A cross-sectional study in which 417 oldest-old persons aged 80 years and older were interviewed, with data collected through the "Health, Welfare and Ageing" survey conducted in two Brazilian cities. Disability was assessed by reporting the need for assistance in Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs). Bivariate and multiple analyses were performed using R statistical software. RESULTS: Food insufficiency in the first years of life had negative repercussions on the disability of oldest old people living in the northeast. On the other hand, in this region, older people have a higher rate of support and live longer with their peers, which may contribute to reducing feelings of loneliness, depressive symptoms, and worse self-perception of health. In the Southeast, financial constraints, subjective poverty, and unmet needs may favour the development of functional limitations between long-lived people. CONCLUSION: Our findings indicate that regional differences in Brazil may influence the disability of older people aged 80 and older. In northeast Brazil, having no partner may contribute to disability for ADLs and IADLs; while, in the longevous population of São Paulo, having a worse self-rated health may contribute to disability for IADLs.

Regional differences regarding the occurrence of falls and associated factors in two populations of Brazilian longevous people.

BACKGROUND: Few studies have explored regional asymmetries and their implications for health policies regarding episodes of falls among the population of ≥80 years old in continental and developing countries like Brazil with deep inequalities and sociocultural differences. OBJECTIVE: To evaluate the occurrence of falls and their association with functional capacity and nutritional status in the longest oldest-old living in two municipalities in the Northeast and Southeast of Brazil. METHODS: This is a cross-sectional study, with primary data collection in which were included in the research seniors aged 80 years or more, of both sexes, belonging to two Brazilian municipalities of discrepant socioeconomic aspects. The dependent variable was the occurrence of falls in the last year. The independent variables were grouped into demographic aspects, functional capacity and nutritional status. To identify variables that contribute to the occurrence of falls, the multiple logistic regression model, adopts a significance level of 5%. RESULTS: The sample was composed of 415 oldest-old adults. From the total, 32.3% reported having fallen in the last year, 24.7% in Brejo dos Santos and 37.8% in São Paulo. Among the former population, the mean value of walking speed for those who had falls was 0.27 m/s and for those who had no occurrence of falls was 0.33 m/s; and, among the seniors from São Paulo, the mean values were 0.51 m/s and 0.58 m/s, respectively. Significant correlations between walking speed and falls were verified for both populations, showing that the lower the walking speed, the higher the predisposition to falls. In the final regression model, the occurrence of falls was associated with moderate balance (OR = 5.28; CI: 1.11-25.18) among the longevous people Brejo dos Santos and with very poor functional performance (OR = 16.09; CI:1.46-177.06) among those from São Paulo. CONCLUSION: The results pointed out a lower prevalence of falls in longevous people from Brejo dos Santos than in those from São Paulo and differences regarding the associated factors, showing heterogeneity between the two populations; indicating the need for public policies and effective programmes aimed at preventing falls based on the maintenance or increase of functional capacity.

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy.

BACKGROUND: Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. METHODS: We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). RESULTS: A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). CONCLUSIONS: Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476 , and Current Controlled Trials number, ISRCTN78818544 .).

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.

BACKGROUND: Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy. METHODS: We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476. FINDINGS: Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63-73) and median amount of prostate-specific antigen of 97 ng/mL (33-315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68-0·84; p<0·0001) but not overall survival (0·92, 0·80-1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3-4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy). INTERPRETATION: Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.

The prevention of arboviral diseases using mobile devices: a preliminary study of the attitudes and behaviour change produced by educational interventions.

OBJECTIVES: In Brazil, the National Policy for Dengue Control seeks to incorporate the lessons of national and international experience in dengue control, emphasising the need for health education activities. The objective of this study was to evaluate and compare knowledge, attitudes and behaviours related to the prevention of arboviruses before and after a two-month educational intervention using a learning platform on mobile devices. METHODS: This quasi-experimental study corresponds to the first phase of the project 'Impact of mobile learning in the prevention and management of complications caused by arboviruses (Zika, Dengue, Chikungunya) - ZIKAMOB', sponsored as part of the British Council Newton Fund. RESULTS: Thirty of the 93 participants were first-year undergraduate university students (36.7% male), and 63 were police officers (84.1% male). The pattern of attitudes and behaviour was very similar in both groups before the intervention. The students changed their attitudes and behaviour (P = 0.032) in relation to their engagements in actions for the prevention of arboviral diseases and several other activities related to house inspections and precautions with water tanks (P < 0.01). However, recycling and surveillance activities were not as effective in changing behaviour. Female participants showed more motivation to participate in preventive activities, but living alone and working were barriers to participation. Individuals who already perform selective waste collection and are cultivating gardens demonstrated both a positive attitude and a positive behaviour towards actions for the prevention of arboviral diseases. CONCLUSION: Mobile learning and behaviour change theories might be successful as the basis for school-based and community-based interventions to avoid arboviruses. These outcomes need to be confirmed in broader future studies.

OBJECTIFS: Au Brésil, la politique nationale de lutte contre la dengue cherche à intégrer les leçons tirées des expériences nationales et internationales en matière de lutte contre la dengue, en insistant sur la nécessité d'activités d'éducation sur la santé. L'objectif de cette étude était d'évaluer et de comparer les connaissances, les attitudes et les comportements liés à la prévention des arbovirus avant et après une intervention éducative de deux mois à l'aide d'une plate-forme d'éducation basée sur des appareils mobiles. MÉTHODES: Cette étude quasi expérimentale correspond à la première phase du projet "Impact de l'éducation mobile dans la prévention et la prise en charge des complications causées par les arbovirus (Zika, Dengue, Chikungunya) - ZIKAMOB", parrainé dans le cadre du British Council Newton Fund. RÉSULTATS: Trente des 93 participants étaient des étudiants de première année d'université (36,7% d'hommes) et 63 étaient des agents de police (84,1% d'hommes). Le modèle des attitudes et de comportement était très similaire dans les deux groupes avant l'intervention. Les étudiants ont changé leurs attitudes et comportements (P = 0,032) en ce qui concerne leur participation à des actions de prévention des maladies à arbovirus et à plusieurs autres activités liées aux inspections des maisons et aux précautions d'utilisation des réservoirs d'eau (P < 0,01). Cependant, les activités de recyclage et de surveillance n'étaient pas aussi efficaces pour le changement de comportement. Les participantes étaient plus motivées à participer aux activités de prévention, mais le fait de vivre seul et de travailler constituait un obstacle à la participation. Les personnes qui effectuent déjà une collecte sélective des déchets et cultivent des jardins ont démontré à la fois une attitude positive et un comportement positif à l'égard des actions de prévention des maladies à arbovirus. CONCLUSION: Les théories sur l'éducation mobile et le changement de comportement pourraient être couronnées de succès en tant que base d'interventions en milieu scolaire et communautaire visant à éviter les arbovirus. Ces résultats doivent être confirmés dans des études supplémentaires plus larges.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Is perception of quality more important than technical quality in patient video cases?

BACKGROUND: The use of video cases to demonstrate key signs and symptoms in patients (patient video cases or PVCs) is a rapidly expanding field. The aims of this study were to evaluate whether the technical quality, or judgement of quality, of a video clip influences a paediatrician's judgment on acuity of the case and assess the relationship between perception of quality and the technical quality of a selection of video clips. METHODS: Participants (12 senior consultant paediatricians attending an examination workshop) individually categorised 28 PVCs into one of 3 possible acuities and then described the quality of the image seen. The PVCs had been converted into four different technical qualities (differing bit rates ranging from excellent to low quality). RESULTS: Participants' assessment of quality and the actual industry standard of the PVC were independent (333 distinct observations, spearmans rho = 0.0410, p = 0.4564). Agreement between actual acuity and participants' judgement was generally good at higher acuities but moderate at medium/low acuities of illness (overall correlation 0.664). Perception of the quality of the clip was related to correct assignment of acuity regardless of the technical quality of the clip (number of obs = 330, z = 2.07, p = 0.038). CONCLUSIONS: It is important to benchmark PVCs prior to use in learning resources as experts may not agree on the information within, or quality of, the clip. It appears, although PVCs may be beneficial in a pedagogical context, the perception of quality of clip may be an important determinant of an expert's decision making.

The anatomy of medical research: US and international comparisons.

IMPORTANCE: Medical research is a prerequisite of clinical advances, while health service research supports improved delivery, access, and cost. Few previous analyses have compared the United States with other developed countries. OBJECTIVES: To quantify total public and private investment and personnel (economic inputs) and to evaluate resulting patents, publications, drug and device approvals, and value created (economic outputs). EVIDENCE REVIEW: Publicly available data from 1994 to 2012 were compiled showing trends in US and international research funding, productivity, and disease burden by source and industry type. Patents and publications (1981-2011) were evaluated using citation rates and impact factors. FINDINGS: (1) Reduced science investment: Total US funding increased 6% per year (1994-2004), but rate of growth declined to 0.8% per year (2004-2012), reaching $117 billion (4.5%) of total health care expenditures. Private sources increased from 46% (1994) to 58% (2012). Industry reduced early-stage research, favoring medical devices, bioengineered drugs, and late-stage clinical trials, particularly for cancer and rare diseases. National Insitutes of Health allocations correlate imperfectly with disease burden, with cancer and HIV/AIDS receiving disproportionate support. (2) Underfunding of service innovation: Health services research receives $5.0 billion (0.3% of total health care expenditures) or only 1/20th of science funding. Private insurers ranked last (0.04% of revenue) and health systems 19th (0.1% of revenue) among 22 industries in their investment in innovation. An increment of $8 billion to $15 billion yearly would occur if service firms were to reach median research and development funding. (3) Globalization: US government research funding declined from 57% (2004) to 50% (2012) of the global total, as did that of US companies (50% to 41%), with the total US (public plus private) share of global research funding declining from 57% to 44%. Asia, particularly China, tripled investment from $2.6 billion (2004) to $9.7 billion (2012) preferentially for education and personnel. The US share of life science patents declined from 57% (1981) to 51% (2011), as did those considered most valuable, from 73% (1981) to 59% (2011). CONCLUSIONS AND RELEVANCE: New investment is required if the clinical value of past scientific discoveries and opportunities to improve care are to be fully realized. Sources could include repatriation of foreign capital, new innovation bonds, administrative savings, patent pools, and public-private risk sharing collaborations. Given international trends, the United States will relinquish its historical international lead in the next decade unless such measures are undertaken.

Identification of a Theory-Practice Gap in the Education of Biomedical Scientists.

Introduction: The Biomedical Scientist (BMS) role is established in healthcare, working in laboratory environments to provide diagnostic testing and to monitor treatment effects on a patients' health. The profession is subject to several professional standards which highlight the importance of working in the best interests of the patient and service user. However, Biomedical Scientists have little or no patient contact. This study aimed to determine how Biomedical Scientists evidence that they meet the professional standards and support the achievement of patient outcomes. Materials and Methods: This study utilised a Delphi method to explore the opinions of professional stakeholders to determine whether there was consensus for how this professional group contributes to patient outcomes and offers evidence that they are working in the best interests of the patient. The qualitative 1st round of the study consisted of focus groups and interviews with staff and students on the BSc Biomedical Science awards, Professional, Statutory and Regulatory body (PSRB) representatives and Biomedical Scientists from the National Health Service (NHS). The first-round responses were analysed using thematic analysis which then generated attitude statements which participants scored using a 5-point Likert scale in the 2nd round. Consensus or divergence of opinion was determined based upon a 70% consensus level within each participant group and overall. Results: Following analysis of the 2nd round data, there was divergence of opinion across all stakeholders, with consensus rates being highest in the Biomedical Scientist group (72.7% of statements reached 70% consensus), followed by the student group (54.5% of statements reached 70% consensus) and lowest in the academic group (40.9% of statements reached 70% consensus). Discussion: This demonstrates a theory-practice gap in both the academic and student groups, suggesting that graduates are insufficiently prepared for their post-graduate role. This gap was particularly evident when discussing topics such as how Biomedical Scientists contribute to patient care, professional registration and working as part of the multi-disciplinary team (MDT). The identification of a theory-practice gap in the education of Biomedical Scientists is a novel finding, indicating that students may graduate with insufficient understanding of the Biomedical Scientist role.

The anatomy of health care in the United States.

Health care in the United States includes a vast array of complex interrelationships among those who receive, provide, and finance care. In this article, publicly available data were used to identify trends in health care, principally from 1980 to 2011, in the source and use of funds ("economic anatomy"), the people receiving and organizations providing care, and the resulting value created and health outcomes. In 2011, US health care employed 15.7% of the workforce, with expenditures of $2.7 trillion, doubling since 1980 as a percentage of US gross domestic product (GDP) to 17.9%. Yearly growth has decreased since 1970, especially since 2002, but, at 3% per year, exceeds any other industry and GDP overall. Government funding increased from 31.1% in 1980 to 42.3% in 2011. Despite the increases in resources devoted to health care, multiple health metrics, including life expectancy at birth and survival with many diseases, shows the United States trailing peer nations. The findings from this analysis contradict several common assumptions. Since 2000, (1) price (especially of hospital charges [+4.2%/y], professional services [3.6%/y], drugs and devices [+4.0%/y], and administrative costs [+5.6%/y]), not demand for services or aging of the population, produced 91% of cost increases; (2) personal out-of-pocket spending on insurance premiums and co-payments have declined from 23% to 11%; and (3) chronic illnesses account for 84% of costs overall among the entire population, not only of the elderly. Three factors have produced the most change: (1) consolidation, with fewer general hospitals and more single-specialty hospitals and physician groups, producing financial concentration in health systems, insurers, pharmacies, and benefit managers; (2) information technology, in which investment has occurred but value is elusive; and (3) the patient as consumer, whereby influence is sought outside traditional channels, using social media, informal networks, new public sources of information, and self-management software. These forces create tension among patient aims for choice, personal care, and attention; physician aims for professionalism and autonomy; and public and private payer aims for aggregate economic value across large populations. Measurements of cost and outcome (applied to groups) are supplanting individuals' preferences. Clinicians increasingly are expected to substitute social and economic goals for the needs of a single patient. These contradictory forces are difficult to reconcile, creating risk of growing instability and political tensions. A national conversation, guided by the best data and information, aimed at explicit understanding of choices, tradeoffs, and expectations, using broader definitions of health and value, is needed.

Quality of Life Measurements from the Patient Perspective: Capturing the Heterogeneity of the Patient Experience in a Standardised Way.

For patients, quality of life is the confluence and interaction of multiple factors related to both the disease and to how life is lived with and beyond the disease. When tasked with completing a quality-of-life questionnaire, patients may well wonder for whose benefit this is, which really needs to be made clear. We discuss some of the issues around quality-of-life questionnaires and the challenge of the heterogeneity of the patient experience. PATIENT SUMMARY: This mini-review discusses quality-of-life measurements from the patient perspective and the need to take account of the patient's life and not just the disease.

Towards a conceptual framework demonstrating the effectiveness of audiovisual patient descriptions (patient video cases): a review of the current literature.

BACKGROUND: Technological advances have enabled the widespread use of video cases via web-streaming and online download as an educational medium. The use of real subjects to demonstrate acute pathology should aid the education of health care professionals. However, the methodology by which this effect may be tested is not clear. METHODS: We undertook a literature review of major databases, found relevant articles relevant to using patient video cases as educational interventions, extracted the methodologies used and assessed these methods for internal and construct validity. RESULTS: A review of 2532 abstracts revealed 23 studies meeting the inclusion criteria and a final review of 18 of relevance. Medical students were the most commonly studied group (10 articles) with a spread of learner satisfaction, knowledge and behaviour tested. Only two of the studies fulfilled defined criteria on achieving internal and construct validity. The heterogeneity of articles meant it was not possible to perform any meta-analysis. CONCLUSIONS: Previous studies have not well classified which facet of training or educational outcome the study is aiming to explore and had poor internal and construct validity. Future research should aim to validate a particular outcome measure, preferably by reproducing previous work rather than adopting new methods. In particular cognitive processing enhancement, demonstrated in a number of the medical student studies, should be tested at a postgraduate level.

The role of distance and transportation in decision making to seek emergency obstetric care among women of reproductive age in south-South Nigeria: A mixed methods study.

OBJECTIVE: To explore the role of transportation in seeking emergency obstetric care among women with obstetric complications. METHODS: A mixed-methods design. The study population comprised women aged 15-49 years who had experience direct obstetric complications and were attending the health facility for care at the time of this study. A total of 318 women completed the questionnaires, and in-depth interviews were held for six women who were purposively selected from the 318 respondents. Both questionnaire and semi-structured interviews were used in collecting data for this study. Quantitative data were analyzed using SPSS using both inferential and bivariate analysis, and a qualitative content analysis was carried out on the qualitative data. RESULTS: Of the 318 respondents, 290 (91.2%) accessed health facilities by motorized transport with 28 (8.8%) on foot. Mode of transportation was related to regularity at prenatal care (P = 0.003), with those who came on foot being regular attenders compared with those that came on motorized transport. CONCLUSION: An efficient and suitable transport system as well as distance are key factors influencing women's role in decision making to seek care.

Health-Related Quality of Life and Associated Factors: Regional Differences Among Oldest-Old in Brazil.

PURPOSE: The aim of this research was to investigate the extent to which socioeconomic and regional differences in Brazil may influence the quality of life. To this end, we examined factors associated with health-related quality of life in two populations of oldest-old people, aged 80 and over: one from the Northeast of Brazil and the other from the Southeast. METHODS: 417 participants aged 80 and over were interviewed face-to-face, 179 from Brejo dos Santos, one of the poorest regions in the Northeast; and 238 from São Paulo, one of the largest urban metropolises in Southeast Brazil. Data, which included socioeconomic and demographic factors, health status, and health-related quality of life, were collected using a structured questionnaire. The dependent variable was determined by the completion rate of the 12-item Short Form Survey and analyzed using multiple logistic regression. RESULTS: Although the population of São Paulo had four times as many long-lived women than men, had better literacy levels, used more medications, and presented a greater prevalence of symptoms suggestive of depression in comparison to the Northeast's population, no difference was observed in the proportion of good physical components among the two populations, 54.3% in Brejo dos Santos' oldest-old and 50.4% in São Paulo's (P = .6272). Quality and quantity of sleep were factors that most affected the health-related quality of life among the oldest-old of Northeast. CONCLUSION: Factors associated with health-related quality of life were different among the oldest-old people of the two locations, thereby corroborating the heterogeneous nature of the longevous population.

Cost-utility analysis of adding abiraterone acetate plus prednisone/prednisolone to long-term hormone therapy in newly diagnosed advanced prostate cancer in England: Lifetime decision model based on STAMPEDE trial data.

Adding abiraterone acetate (AA) plus prednisolone (P) to standard of care (SOC) improves survival in newly diagnosed advanced prostate cancer (PC) patients starting hormone therapy. Our objective was to determine the value for money to the English National Health Service (NHS) of adding AAP to SOC. We used a decision analytic model to evaluate cost-effectiveness of providing AAP in the English NHS. Between 2011-2014, the STAMPEDE trial recruited 1917 men with high-risk localised, locally advanced, recurrent or metastatic PC starting first-line androgen-deprivation therapy (ADT), and they were randomised to receive SOC plus AAP, or SOC alone. Lifetime costs and quality-adjusted life-years (QALYs) were estimated using STAMPEDE trial data supplemented with literature data where necessary, adjusting for baseline patient and disease characteristics. British National Formulary (BNF) prices (£98/day) were applied for AAP. Costs and outcomes were discounted at 3.5%/year. AAP was not cost-effective. The incremental cost-effectiveness ratio (ICER) was £149,748/QALY gained in the non-metastatic (M0) subgroup, with 2.4% probability of being cost-effective at NICE's £30,000/QALY threshold; and the metastatic (M1) subgroup had an ICER of £47,503/QALY gained, with 12.0% probability of being cost-effective. Scenario analysis suggested AAP could be cost-effective in M1 patients if priced below £62/day, or below £28/day in the M0 subgroup. AAP could dominate SOC in the M0 subgroup with price below £11/day. AAP is effective for non-metastatic and metastatic disease but is not cost-effective when using the BNF price. AAP currently only has UK approval for use in a subset of M1 patients. The actual price currently paid by the English NHS for abiraterone acetate is unknown. Broadening AAP's indication and having a daily cost below the thresholds described above is recommended, given AAP improves survival in both subgroups and its cost-saving potential in M0 subgroup.