A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

Changes in the structure of seed dispersal networks when including interaction outcomes from both plant and animal perspectives

Interaction frequency is the most common currency in quantitative ecological networks, although interaction quality can also affect benefits provided by mutualisms. Here, we evaluate if interaction quality can modify network topology, species' role and whether such changes affect community vulnerability to species loss. We use a well-examined study system (bird–lizard and fleshy-fruited plants in the ‘thermophilous' woodland of the Canary Islands) to compare network and species-level metrics from a network based on fruit consumption rates (interaction frequency, IF), against networks reflecting functional outcomes: a seed dispersal effectiveness network (SDE) quantifying recruitment, and a fruit resource provisioning network (FRP), accounting for the nutrient supply of fruits. Nestedness decreased in the FRP and the SDE networks, due to the lack of association between fruit consumption rates and 1) nutrient content and; 2) recruitment at the seed deposition sites, respectively. The FRP network showed lower niche overlap due to resource use complementarity among frugivores. Interaction evenness was lower in the SDE network, in response to a higher dominance of lizards in the recruitment of heliophilous species. Such changes, however, did not result in enhanced vulnerability against extinctions. At the plant species level, strength changed in the FRP network in frequently consumed or highly nutritious species. The number of effective partners decreased for species whose seeds were deposited in unsuitable places for recruitment. In frugivores, strength was consistent across networks (SDE vs IF), showing that consumption rates outweighed differences in dispersal quality. In the case of lizards, the increased importance of nutrient-rich species resulted in a higher number of effective partners. Our work shows that although frequency strongly impacts interaction effects, accounting for quality improves our inferences about interaction assembly and species role. Thus, future studies including interaction outcomes from both partners' perspectives will provide valuable insights about the net effects of mutualistic interactions.This study is framed within projects CGL2007-61165/BOS and CGL2017-88122-P from the Spanish Ministry of Science and supported by FEDER funds from the European Union. We are grateful to Guido Jones, currently funded by the Cabildo de Tenerife under the TFinnova Programme supported by MEDI and FDCAN, for revising the English and making useful recommendations to improve it. We are especially grateful to Airam Rodríguez, David Padilla, Beatriz Rumeu, Daniel González, Benito Pérez, Yurena Gavilán, Patricia Marrero, Elsa Bonnaud and Concepción Nieves, who helped at different stages of the study. AGC benefitted from a JAE-PRE fellowship from the Spanish National Research Council (CSIC) and was funded by the island council, Cabildo de Tenerife, under the identification mark “Tenerife 2030” (P. INNOVA 2016-2021).Peer reviewe

The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside

At the beginning of the twenty-first century, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues. The altered metabolism of cancers, an essential hallmark for their progression, also became their Achilles heel by facilitating 3BP's selective entry and specific targeting. Treatment with 3BP has been administered in several cancer type models both in vitro and in vivo, either alone or in combination with other anticancer therapeutic approaches. These studies clearly demonstrate 3BP's broad action against multiple cancer types. Clinical trials using 3BP are needed to further support its anticancer efficacy against multiple cancer types thus making it available to more than 30 million patients living with cancer worldwide. This review discusses current knowledge about 3BP related to cancer and discusses also the possibility of its use in future clinical applications as it relates to safety and treatment issues.This work was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569)funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). João Azevedo-Silva received a fellowship from the Portuguese government from the FCT through FSE (Fundo Social Europeu) and POPH (Programa Operacional Potencial Humano) [grant number SFRH/BD/76038/2011]. Co-author Peter L.Pedersen was supported by NIH grant NCICAl0951 for many years for cancer research that led to a number of the findings described in this review.info:eu-repo/semantics/publishedVersio