Background
The motor speech disorder, dysarthria, is common in cerebral palsy. The Speech Systems Approach therapy programme, which focuses on controlling breath supply and speech rate, has increased ...children’s intelligibility.
Objective
To ascertain if increased intelligibility is due to better differentiation of the articulation of individual consonants in words spoken in isolation and in connected speech.
Design
Secondary analysis.
Setting
University.
Participants
Forty-two children with cerebral palsy and dysarthria aged 5–18 years, Gross Motor Function Classification System I–V.
Intervention
The Speech Systems Approach is a motor learning therapy delivered to individuals by a speech and language therapist in 40-minute sessions, three times per week for 6 weeks. Intervention focuses on production of a strong, clear voice and speaking at a steady rate. Practice changes from single words to increasingly longer utterances in tasks with increasing cognitive load.
Main outcome measures
Unfamiliar listeners’ identification of singleton consonants (e.g.
n
a
p
) and clusters of consonants (e.g.
st
air, e
nd
) at the start and end of words when hearing single words in forced choice tasks and connected speech in free transcription tasks. Acoustic measures of sound intensity and duration.
Data sources
Data collected at 1-week pre- and 1-week post-therapy from three studies: two interrupted time series design, one feasibility randomised controlled trial.
Results
Word initial and word final singleton consonants and consonant clusters were better identified post-therapy. The extent of improvement differed across word initial and word final singleton consonant subtypes. Improvement was greater for single words than connected speech. Change in sound identification varied across children, particularly in connected speech. Sound intensity and duration increases also were inconsistent.
Limitations
The small sample size did not allow for analysis of cerebral palsy type. Acoustic data were not available for all children, limiting the strength of conclusions that can be drawn. The different but phonetically balanced word lists, used in the original research, created variability in single words spoken across recordings analysed. Low frequencies of plosives, fricatives and affricates necessitated their combination for analysis preventing investigation of the effect of specific consonants. Connected speech was spontaneous, again creating variability within the data analysed. The estimated effects of therapy may therefore be partially explained by differences in the spoken language elicited.
Conclusions
The Speech Systems Approach helped children generate greater breath supply and a steady rate, leading to increased intensity and duration of consonant sounds in single words, thereby aiding their identification by listeners. Transfer of the motor behaviour to connected speech was inconsistent.
Future work
Refining the Speech Systems Approach to focus on connected speech early in the intervention. Personalisation of cues according to perceptual and acoustic speech measures. Creation of a battery of measures that can be repeated across children and multiple recordings.
Study registration
This trial is registered as Research Registry 6117.
Funding
This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme (NIHR130967) and will be published in full in
Efficacy and Mechanism Evaluation
; Vol. 10, No. 4. See the NIHR Journals Library website for further project information.
To resolve the problem of ageist attitudes in organizational contexts, the psychological processes that contribute to their endorsement must be investigated. We suggest that lay theories of aging ...(essentialist beliefs about cognitive aging, EBCA), fixed versus growth mindsets, and lay theories of time (LTT, perceptions of time as change versus. repetition) represent a set of beliefs linked to ageist attitudes toward older workers. We also propose that relationships between these beliefs and ageism are mediated by stereotypical perceptions of older workers. In a pilot study, we constructed a measure of ageist attitudes toward older workers (AATOW). In the main study, we surveyed 166 younger workers (18–30 years old, employed full‐time), measuring EBCA, mindsets, LTT, age‐related stereotypes, and AATOW. The results demonstrated that there were significant relationships between EBCA, fixed mindset, LTT, and ageist attitudes. The relationships between EBCA and ageism, and mindsets and ageism were mediated by perceptions of older workers as not adaptable, while the relationship between LTT and ageism was not mediated by age‐related stereotypes. Implications for organizational efforts to nurture an age‐inclusive intergenerational workforce are discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis ...affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment.
To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care.
Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded.
Nine NHS head and neck cancer sites in England and Wales.
A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy.
Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm
, irradiance 50 mW/cm
, exposure time 60 seconds and fluence 3 J/cm
. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner.
The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome.
A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm,
= 44; sham arm,
= 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm.
The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth.
This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services.
Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research.
This trial is registered as ISRCTN14224600.
This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.
ObjectivesWe consider expert opinion and its incorporation into a planned meta-analysis as a way of adjusting for anticipated publication bias. We conduct an elicitation exercise among eligible ...British Gynaecological Cancer Society (BGCS) members with expertise in gynaecology.DesignExpert elicitation exercise.SettingBGCS.ParticipantsMembers of the BGCS with expertise in gynaecology.MethodsExperts were presented with details of a planned prospective systematic review and meta-analysis, assessing overall survival for the extent of excision of residual disease (RD) after primary surgery for advanced epithelial ovarian cancer. Participants were asked views on the likelihood of different studies (varied in the size of the study population and the RD thresholds being compared) not being published. Descriptive statistics were produced and opinions on total number of missing studies by sample size and magnitude of effect size estimated.ResultsEighteen expert respondents were included. Responders perceived publication bias to be a possibility for comparisons of RD <1 cm versus RD=0 cm, but more so for comparisons involving higher volume suboptimal RD thresholds. However, experts’ perceived publication bias in comparisons of RD=0 cm versus suboptimal RD thresholds did not translate into many elicited missing studies in Part B of the elicitation exercise. The median number of missing studies estimated by responders for the main comparison of RD<1 cm versus RD=0 cm was 10 (IQR: 5–20), with the number of missing studies influenced by whether the effect size was equivocal. The median number of missing studies estimated for suboptimal RD versus RD=0 cm was lower.ConclusionsThe results may raise awareness that a degree of scepticism is needed when reviewing studies comparing RD <1 cm versus RD=0 cm. There is also a belief among respondents that comparisons involving RD=0 cm and suboptimal thresholds (>1 cm) are likely to be impacted by publication bias, but this is unlikely to attenuate effect estimates in meta-analyses.
Objectives
We systematically reviewed how investigators argued for and justified the validity of their instrumental variables (IV) in clinical studies of dementia and neurodegenerative disease.
...Methods
We included studies using IV analysis with observational data to investigate causal effects in clinical research studies of dementia and neurodegenerative disease. We reported the subject‐matter argumentation, falsification test, and study design strategies used to satisfy the three assumptions of a valid IV: relevance, exclusion restriction, and exchangeability.
Results
Justification for the relevance assumption was performed in all 12 included studies, exclusion restriction in seven studies, and exchangeability in nine studies. Two subject‐matter argumentation strategies emerged from seven studies on the relevance of their IV. All studies except one provided quantitative evidence for the strength of the association between the IV and exposure variable. Four argumentation strategies emerged for exclusion restriction from six studies. Four falsification tests were performed across three studies. Three argumentation strategies emerged for exchangeability across four studies. Nine falsification tests were performed across nine studies. Two notable study design strategies were reported.
Conclusion
Our results reinforce IV analysis as a feasible option for clinical researchers in dementia and neurodegenerative disease by clarifying known strategies used to validate an IV.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
IntroductionSkeletal muscle dysfunction is central to both sarcopenia and physical frailty, which are associated with a wide range of adverse outcomes including falls and fractures, longer hospital ...stays, dependency and the need for care. Resistance training may prevent and treat sarcopenia and physical frailty, but not everyone can or wants to exercise. Finding alternatives is critical to alleviate the burden of adverse outcomes associated with sarcopenia and physical frailty. This trial will provide proof-of-concept evidence as to whether metformin can improve physical performance in older people with sarcopenia and physical prefrailty or frailty.Methods and analysisMET-PREVENT is a parallel group, double-blind, placebo-controlled proof-of-concept trial. Trial participants can participate from their own homes, including completing informed consent and screening assessments. Eligible participants with low grip strength or prolonged sit-to-stand time together with slow walk speed will be randomised to either oral metformin hydrochloride 500 mg tablets or matched placebo, taken three times a day for 4 months. The recruitment target is 80 participants from two secondary care hospitals in Newcastle and Gateshead, UK. Local primary care practices will act as participant identification centres. Randomisation will be performed using a web-based minimisation system with a random element, balancing on sex and baseline walk speed. Participants will be followed up for 4 months post-randomisation, with outcomes collected at baseline and 4 months. The primary outcome measure is the four metre walk speed at the 4-month follow-up visit.Ethics and disseminationThe trial has been approved by the Liverpool NHS Research Ethics Committee (20/NW/0470), the Medicines and Healthcare Regulatory Authority (EudraCT 2020-004023-16) and the UK Health Research Authority (IRAS 275219). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community.Trial registration numberISRCTN29932357.
Abstract
Background
Critically unwell babies in intensive care units may develop acute renal failure. Options for renal replacement therapy are limited by their small size and available technology.
...Objectives
To determine the clinical efficacy, outcomes and safety profile of the NIDUS
®
(a novel infant haemodialysis device) for babies under 8 kg, compared with current renal replacement therapy.
Design
A clinical investigation using a non-blinded cluster stepped wedge design with paediatric intensive care units randomised to sequences.
Setting
Paediatric intensive care units in six UK hospitals.
Participants
Children under 8 kg who required renal replacement therapy for fluid overload or biochemical disturbance.
Interventions
Continuous renal replacement therapy was provided by the usual methods: peritoneal dialysis and continuous haemofiltration (during control periods) and by the NIDUS (during intervention periods), a novel device designed for babies with a smaller circuit and filter and volumetric control of ultrafiltration.
Main outcome measures
Primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances, accuracy of reported ultrafiltration and mortality.
Data sources
Bedside study data collected by weighing bags of fluid entering and leaving the device were entered into the study database along with case descriptors. Some secondary outcome data was collected via the Paediatric Intensive Care Audit Network.
Results
Ninety-seven participants were recruited by study closure, 62 to control and 35 to intervention. The primary outcome was obtained from 62 control but only 21 intervention patients, largely because of technical difficulties using NIDUS. The analysis comparing the available primary outcomes showed that ultrafiltration with NIDUS was closer to that prescribed than with control: standard deviations controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71);
p
= 0.018.
The mean clearances for creatinine, urea and phosphate were lower on peritoneal dialysis than NIDUS, which were in turn lower than continuous veno-venous haemofiltration. The variability in the clearances was in the same order.
Of the 62 control patients, 10 died (2/62 on peritoneal dialysis; 7/13 on continuous haemofiltration) before discharge from paediatric intensive care unit (16%), compared with 12 out of 35 (34%) in the NIDUS group:
p
= 0.04, 95% confidence interval for difference (0 to 36%).
Harms
No important adverse events occurred and the NIDUS has an acceptable safety profile compared with other renal replacement therapies in this critically ill population with multi-organ failure. Mortality was lowest for Peritoneal Dialysis, highest for continuous haemofiltration, with the NIDUS in-between. Only one serious adverse device event which was reported to the Medicines and Healthcare products Regulatory Agency.
Conclusions
NIDUS works effectively, delivering appropriate blood clearances and accurate, controllable fluid removal (ultrafiltration), indicating that it has an important place alongside other dialysis modalities for infant renal replacement therapy.
Future work
Findings from this study indicate some modifications are required to NIDUS to improve usability. Further studies on use of the NIDUS device in other populations of babies for example those with chronic renal failure, and long-term outcomes are required.
Trial registration
This trial is registered as ISRCTN 13787486.
Funding
This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in
Efficacy and Mechanism Evaluation
; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information.
Background: Studies of patients with Alzheimer's disease (AD) have observed that neuropsychiatric symptoms (NPS) tend to co‐occur as neuropsychiatric syndromes and have generally shown mixed results ...regarding the number and composition of syndromes. We systematically reviewed how neuropsychiatric syndromes in AD have been defined and compared the different published definitions in a pooled sample of AD patients using meta‐analytic structural equation modeling (MASEM).
Methods: Studies examining the factor structure of the Neuropsychiatric Inventory (NPI) and published from 1994 to 2021 were included. We contacted the corresponding authors of eligible studies for correlation coefficients between NPI items. We pooled correlations under a random effects MASEM model and fitted and compared measurement models from published studies to identify a best‐fitting model.
Results: Twenty‐five studies were included in the systematic review, and correlations were obtained from seven studies for MASEM. For the NPI‐10 (seven studies, n = 5185), a five‐factor structure was found to have a good fit to the data. For the NPI‐12 (four studies, n = 2397), we were unable to identify a factor structure that displayed a good model fit.
Conclusion: This systematic review and meta‐analysis contribute to the development of a theoretical model of neuropsychiatric syndromes in AD and reveals the barriers that accompany MASEM methodology.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
IntroductionObservational studies represent an alternative to estimate real-world causal effects in the absence of available randomised controlled trials (RCTs). Target trial emulation is a framework ...for the application of RCT design principles to emulate a hypothetical open-label RCT (the hypothetical target trial) using existing observational data as the primary data source as opposed to the prospective recruitment and measurement of randomised units. The aim of this systematic review is to investigate the practices of studies applying the target trial emulation framework to evaluate the effectiveness of interventions.Methods and analysisWe will systematically search in Medline (via Ovid), Embase (via Ovid, entries from medRxiv are included), PsycINFO (via Ovid), SCOPUS, Web of Science, Cochrane Library, the ISRCTN registry and ClinicalTrials.gov for all study reports and protocols which used the trial emulation framework (without time restriction). We will extract information concerning study design, data source, analysis, results, interpretation and dissemination. Two reviewers will perform study selection, data extraction and quality assessment. Disagreements between reviewers will be resolved by a third reviewer. A narrative approach will be used to synthesise and report qualitative and quantitative data. Reporting of the review will be informed by Preferred Reporting Items for Systematic Review and Meta-Analysis guidance (PRISMA).Ethics and disseminationEthical approval is not required as it is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations.
Our knowledge of immune-mediated inflammatory disease (IMID) aetiology and pathogenesis has improved greatly over recent years, however, very little is known of the factors that trigger disease ...relapses (flares), converting diseases from inactive to active states. Focussing on rheumatoid arthritis (RA), the challenge that we will address is why IMIDs remit and relapse. Extrapolating from pathogenetic factors involved in disease initiation, new episodes of inflammation could be triggered by recurrent systemic immune dysregulation or locally by factors within the joint, either of which could be endorsed by overarching epigenetic factors or changes in systemic or localised metabolism.
The BIO-FLARE study is a non-randomised longitudinal cohort study that aims to enrol 150 patients with RA in remission on a stable dose of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), who consent to discontinue treatment. Participants stop their DMARDs at time 0 and are offered an optional ultrasound-guided synovial biopsy. They are studied intensively, with blood sampling and clinical evaluation at weeks 0, 2, 5, 8, 12 and 24. It is anticipated that 50% of participants will have a disease flare, whilst 50% remain in drug-free remission for the study duration (24 weeks). Flaring participants undergo an ultrasound-guided synovial biopsy before reinstatement of previous treatment. Blood samples will be used to investigate immune cell subsets, their activation status and their cytokine profile, autoantibody profiles and epigenetic profiles. Synovial biopsies will be examined to profile cell lineages and subtypes present at flare. Blood, urine and synovium will be examined to determine metabolic profiles. Taking into account all generated data, multivariate statistical techniques will be employed to develop a model to predict impending flare in RA, highlighting therapeutic pathways and informative biomarkers. Despite initial recruitment to time and target, the SARS-CoV-2 pandemic has impacted significantly, and a decision was taken to close recruitment at 118 participants with complete data.
This study aims to investigate the pathogenesis of flare in rheumatoid arthritis, which is a significant knowledge gap in our understanding, addressing a major unmet patient need.
The study was retrospectively registered on 27/06/2019 in the ISRCTN registry 16371380 .
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