Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.
Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland.
People with multiple sclerosis (pwMS) frequently present with deficits in binaural processing used for sound localization. This study examined spatial release from speech-on-speech masking in pwMS, which involves binaural processing and additional higher level mechanisms underlying streaming, such as spatial attention. 26 pwMS with mild severity (Expanded Disability Status Scale score <3) and 20 age-matched controls listened via headphones to pre-recorded sentences from a standard list presented simultaneously with eight-talker babble.
View Article and Find Full Text PDFBackground: STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival.
Methods: Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy.
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.
PLoS One
June 2022
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.
View Article and Find Full Text PDFAbiraterone 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.
View Article and Find Full Text PDFBackground: Apraxia and action disorganization syndrome (AADS) after stroke can disrupt activities of daily living (ADL). Occupational therapy has been effective in improving ADL performance, however, inclusion of multiple tasks means it is unclear which therapy elements contribute to improvement. We evaluated the efficacy of a task model approach to ADL rehabilitation, comparing training in making a cup of tea with a stepping training control condition.
View Article and Find Full Text PDFBackground: Fractionated fat has been shown to promote dermal regeneration; however, the use of fat grafting for reconstruction of soft-tissue defects is limited because of volume loss over time. The authors have developed a novel approach for engineering of vascularized soft tissue using an injectable nanofiber hydrogel composite enriched with fractionated fat.
Methods: Fractionated fat was generated by emulsification of groin fat pads from rats and mixed in a 3:1 ratio with nanofiber hydrogel composite (nanofiber hydrogel composite with fractionated fat).
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.
Exoskeletons that assist the hip, knee, and ankle joints have begun to improve human mobility, particularly by reducing the metabolic cost of walking. However, direct comparisons of optimal assistance of these joints, or their combinations, have not yet been possible. Assisting multiple joints may be more beneficial than the sum of individual effects, because muscles often span multiple joints, or less effective, because single-joint assistance can indirectly aid other joints.
View Article and Find Full Text PDFPurpose: Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices.
Methods: A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC.
Habitat loss from land-use change is one of the top causes of declines in wildlife species of concern. As such, it is critical to assess and reassess habitat suitability as land cover and anthropogenic features change for both monitoring and developing current information to inform management decisions. However, there are obstacles that must be overcome to develop consistent assessments through time.
View Article and Find Full Text PDFBackground: Moderate hypofractionation is the recommended standard of care for localised prostate cancer following the results of trials including Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP). Evaluation of long-term patient-reported outcomes (PROs) is important to confirm safety and enhance patient information.
Objective: To determine whether 5-yr PROs from the CHHiP quality of life (QoL) substudy confirm 2-yr findings and assess patterns over follow-up.
There is a need for reliable and objective measures of early and mild symptomology in multiple sclerosis (MS), as deficits can be subtle and difficult to quantify objectively in patients without overt physical deficits. We hypothesized that a speech-in-noise (SiN) task would be sensitive to demyelinating effects on precise neural timing and diffuse higher-level networks required for speech intelligibility, and therefore be a useful tool for monitoring sensory and cognitive changes in early MS. The objective of this study was to develop a SiN task for clinical use that sensitively monitors disease activity in early (<5 years) and late (>10 years) stages of MS subjects with mild severity [Expanded Disability Status Scale (EDSS) score < 3].
View Article and Find Full Text PDFThe most complex interactions between human beings occur through speech, and often in the presence of background noise. Understanding speech in noisy environments requires the integrity of highly integrated and widespread auditory networks likely to be impacted by multiple sclerosis (MS) related neurogenic injury. Despite the impact auditory communication has on a person's ability to navigate the world, build relationships, and maintain employability; studies of speech-in-noise (SiN) perception in people with MS (pwMS) have been minimal to date.
View Article and Find Full Text PDFMult Scler Relat Disord
January 2021
Background: Multiple Sclerosis (MS) pathology is likely to disrupt central auditory pathways, thereby affecting an individual's ability to discriminate speech from noise. Despite the importance of speech discrimination in daily communication, it's characterization in the context of MS remains limited. This cross-sectional study evaluated speech discrimination in MS under "real world" conditions where sentences were presented in ecologically valid multi-talker speech or broadband noise at several signal-to-noise ratios (SNRs).
View Article and Find Full Text PDFTo develop a novel approach for tissue engineering of soft-tissue flaps suitable for free microsurgical transfer, using an injectable nanofiber hydrogel composite (NHC) vascularized by an arteriovenous (AV) loop. A rat AV loop model was used for tissue engineering of vascularized soft-tissue flaps. NHC or collagen-elastin (CE) scaffolds were implanted into isolation chambers together with an AV loop and explanted after 15 days.
View Article and Find Full Text PDFAn injury to the spinal cord causes long-lasting loss of nervous tissue because endogenous nervous tissue repair and regeneration at the site of injury is limited. We engineered an injectable nanofiber-hydrogel composite (NHC) with interfacial bonding to provide mechanical strength and porosity and examined its effect on repair and neural tissue regeneration in an adult rat model of spinal cord contusion. At 28 days after treatment with NHC, the width of the contused spinal cord segment was 2-fold larger than in controls.
View Article and Find Full Text PDFBackground And Objectives: Children and pregnant women use 75% of the blood supply in sub-Saharan Africa (SSA) but face widespread blood shortages. To increase safe blood supply, Africa-specific evidence and strengthened capacity for transfusion research are needed. Our study analysed seven years of SSA transfusion publications, compared researched topics against priorities and enumerated SSA transfusion research collaborations.
View Article and Find Full Text PDFPrimary aldosteronism (PA) is a potentially reversible cause of uncontrolled hypertension. Early diagnosis and timely management of PA can prevent end-organ damage. Aldosteronoma Resolution Score (ARS) is a useful tool to predict cure rates and resolution of hypertension after adrenalectomy.
View Article and Find Full Text PDFBackground: Abiraterone acetate received licencing for use in only "high-risk" metastatic hormone-naïve prostate cancer (mHNPC) following the LATITUDE trial findings. However, a "risk"-related effect was not seen in the STAMPEDE trial. There remains uncertainty as to whether men with LATITUDE "low-risk" M1 disease benefit from androgen deprivation therapy (ADT) combined with abiraterone acetate and prednisolone (AAP).
View Article and Find Full Text PDFThe ability to treat large peripheral nerve injuries may be greatly advanced if an accessible source of human myelinating cells is identified, as it overcomes one of the major limitations of acellular or synthetic nerve guides compared with autografts, the gold standard for large defect repair. Methods to derive oligodendrocyte precursor cells (OPCs) from human pluripotent stem cells have advanced to the point where they have been shown capable of myelination and are being evaluated in clinical trials. Here, we test the hypothesis that OPCs can survive and remyelinate axons in the peripheral nervous system during a repair process.
View Article and Find Full Text PDFBackground: The purpose of this study was to assess the efficacy of biodegradable, electrospun poly(ε-caprolactone) nanofiber nerve conduits in improving nerve regeneration.
Methods: The authors used a rat forelimb chronic denervation model to assess the effects of poly(ε-caprolactone) conduits on improving nerve regeneration and upper extremity function. Three groups of rats were examined: (1) negative-control animals (n = 5), which underwent 8 weeks of median nerve chronic denervation injury followed by repair with no conduit; (2) experimental animals (n = 5), which underwent 8 weeks of median nerve chronic denervation followed by repair and poly(ε-caprolactone) nerve conduit wrapping of the nerve coaptation site; and (3) positive-control animals (n = 5), which were naive controls.
Eur Urol Oncol
December 2018
Background: Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources.
Objective: To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting.
Functional recovery following nerve injury declines when target re-innervation is delayed. Currently, no intervention exists to improve outcomes after prolonged denervation. We explored the neuroregenerative effects of glial cell line-derived neurotrophic factor (GDNF) and chondroitinase (CDN) in a chronic denervation animal model.
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