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

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Limitations of feedforward control in multiple-phase steering movements

When attempting to perform bi-phasic steering movements (such as a lane change) in the absence of visual and inertial feedback, drivers produce a systematic heading error in the direction of the lane change (Wallis et al., Curr Biol 12(4):295–299, 2002; J Exp Psychol Hum Percept Perform 33(55):1127–1144, 2007). Theories of steering control which employ exclusively open-loop control mechanisms cannot accommodate this finding. In this article we show that a similar steering error occurs with obstacle avoidance, and offer compelling evidence that it stems from a seemingly general failure of human operators to correctly internalise the dynamics of the steering wheel. With respect to lateral position, the steering wheel is an acceleration control device, but we present data indicating that drivers treat it as a rate control device. Previous findings from Wallis et al. can be explained the same way. Since an open-loop control mechanism will never succeed when the dynamics of the controller are internalised improperly, we go on to conclude that regular, appropriately timed sensory feedback—predominantly from vision—is necessary for regulating heading, even during well-practiced, everyday manoeuvres such as lane changing and obstacle avoidance

The face-in-the-crowd effect: When angry faces are just cross(es)

A common theme running through much of the visual recognition literature is that faces are special. Many studies now describe evidence for the idea that faces are processed in a dedicated center in cortex. Studies have also argued for the presence of evolutionarily expedient pathways dedicated to the processing of certain facial expressions. Evidence for this proposal comes largely from visual search tasks which have established that threatening expressions are more rapidly detected than other expressions: the 'face-in-the-crowd effect'. One open criticism of this effect is that it may be due to low-level visual artifacts, rather than biological preparedness. One attempt at controlling low-level differences has been to use schematic line-drawing versions of faces. This study aimed to discover if there might be alternative issues with schematic stimuli. The first study replicated the face-in-the-crowd threat advantage for schematic faces, but also measured a comparable effect using stimuli comprised of obliquely oriented lines. Similar results were achieved with these stimuli rotated, which had the effect of removing any residual resemblance to a face. The results suggest that low-level features probably underlie the face-in-the-crowd effect described for schematic face images, thereby undermining evidence for a search advantage for specific facial expressions

Searching for Faces is Easiest when they are Cross(es)

It has been suggested that certain facial expressions are subject to enhanced processing to maximize the speed and accuracy with which humans locate individuals posing an imminant threat. Evidence supporting this proposal comes largely from visual search tasks which have demonstrated that threatening expressions are more rapidly detected than nonthreatening ones. An open criticism of this effect is that it may be due to low-level visual artifacts, rather than biological preparedness. One successful approach for controlling low-level, image-based differences has been to use schematic faces (simplified line drawings). We report experiments aimed at discovering whether the enhanced processing of threatening schematic faces, might also be due to low-level features. The first study replicated the standard threat search advantage, but also measured an effect using similar stimuli comprised of obliquely oriented lines. The effect was also present with these stimuli rotated, a manipulation which served to remove any residual resemblance the abstract images had to a face. The results suggest that low-level features underlie the search advantage for angry, schematic faces, thereby undermining a key source of evidence of a search advantage for specific facial expressions

Modelling driver behaviour towards innovative warning devices at railway level crossings

Improving safety at railway level crossings is costly and as funds are often limited, it is important to search for cost-effective, evidence-based solutions. The effect that the many existing alternative systems have on driver behaviour is not always known. This paper compares driver behaviour towards two novel warning devices (rumble strips and in-vehicle audio warning) at railway level crossings with two conventional warning devices (flashing light and stop sign). Regression models were developed to reflect driver's responses towards the four different types of devices based on data collected from a driving simulation experiment. The regression models include a binary choice model for predicting the probability of a driver stopping or driving through a railway crossing, as well as mixed regression models for predicting the moment at which a driver will produce specific behavioural responses before stopping at a crossing (e.g. initiation of accelerator release and application of foot-pedal brake). Violation results indicated the active systems produced much higher levels of driver compliance than passive devices. Contributing factors, such as age, gender, speed and types of warning devices were found significant at different approach stages to the level crossings. With the application of such behavioural models and traffic conflict techniques in microscopic simulation tools, traffic safety indicators, such as collision likelihood and time-to-collision can be estimated. From these, relative safety comparisons for the different traffic devices are derived