ResearchPad - 1713 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[G-CSF (filgrastim) treatment for amyotrophic lateral sclerosis: protocol for a phase II randomised, double-blind, placebo-controlled, parallel group, multicentre clinical study (STEMALS-II trial)]]> https://www.researchpad.co/article/elastic_article_9140 Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurological disorder characterised by a selective degeneration of motor neurons (MNs). Stem cell transplantation is considered as a promising strategy in neurological disorders therapy and the possibility of inducing bone marrow cells (BMCs) to circulate in the peripheral blood is suggested to investigate stem cells migration in degenerated ALS nerve tissues where potentially repair MN damage. Granulocyte-colony stimulating factor (G-CSF) is a growth factor which stimulates haematopoietic progenitor cells, mobilises BMCs into injured brain and it is itself a neurotrophic factor for MN. G-CSF safety in humans has been demonstrated and many observations suggest that it may affect neural cells. Therefore, we decided to use G-CSF to mobilise BMCs into the peripheral circulation in patients with ALS, planning a clinical trial to evaluate the effect of G-CSF administration in ALS patients compared with placebo.Methods and analysisSTEMALS-II is a phase II multicentre, randomised double-blind, placebo-controlled, parallel group clinical trial on G-CSF (filgrastim) and mannitol in ALS patients. Specifically, we investigate safety, tolerability and efficacy of four repeated courses of intravenous G-CSF and mannitol administered in 76 ALS patients in comparison with placebo (indistinguishable glucose solution 5%). We determine increase of G-CSF levels in serum and cerebrospinal fluid as CD34+ cells and leucocyte count after treatment; reduction in ALS Functional Rating Scale-Revised Score, forced vital capacity, Scale for Testing Muscle Strength Score and quality of life; the adverse events/reactions during the treatment; changes in neuroinflammation biomarkers before and after treatment.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Azienda Ospedaliera Universitaria ‘Città della Salute e della Scienza’, Torino, Italy. Results will be presented during scientific symposia or published in scientific journals.Trial registration numberEudract 2014-002228-28. ]]> <![CDATA[Usual care and a self-management support programme versus usual care and a relaxation programme for people living with chronic headache disorders: a randomised controlled trial protocol (CHESS)]]> https://www.researchpad.co/article/N66380eea-f76b-460e-8d51-efd77e352582 Chronic headaches are poorly diagnosed and managed and can be exacerbated by medication overuse. There is insufficient evidence on the non-pharmacological approaches to helping people living with chronic headaches.Methods and analysisChronic Headache Education and Self-management Study is a pragmatic randomised controlled trial to test the effectiveness and cost-effectiveness of a self-management education support programme on top of usual care for patients with chronic headaches against a control of usual care and relaxation. The intervention is a 2-day group course based on education, personal reflection and a cognitive behavioural approach, plus a nurse-led one-to-one consultation and follow-up over 8 weeks. We aim to recruit 689 participants (356 to the intervention arm and 333 to the control) from primary care and self-referral in London and the Midlands. The trial is powered to show a difference of 2.0 points on the Headache Impact Test, a patient-reported outcome measure at 12 months post randomisation. Secondary outcomes include health related quality of life, self-efficacy, social activation and engagement, anxiety and depression and healthcare utilisation. Outcomes are being measured at 4, 8 and 12 months. Cost-effectiveness will be expressed in terms of incremental cost per quality-adjusted life year gained.Ethics and disseminationThis trial will provide data on effectiveness and cost-effectiveness of a self-management support programme for chronic headaches. The results will inform commissioning of services and clinical practice. North West – Greater Manchester East Research Ethics Committee have approved the trial. The current protocol version is 3.6 date 7 March 2019.Trial registration numberISRCTN79708100. ]]> <![CDATA[Protocol for a feasibility study of OnTrack: a digital system for upper limb rehabilitation after stroke]]> https://www.researchpad.co/article/N94dd4ff3-7b00-423a-be69-a4ad53b55729

Introduction

Arm weakness is a common problem after stroke (affecting 450 000 people in the UK) leading to loss of independence. Repetitive activity is critical for recovery but research shows people struggle with knowing what or how much to do, and keeping track of progress. Working with more than 100 therapists (occupational therapists and physiotherapists) and patients with stroke, we codeveloped the OnTrack intervention—consisting of software for smart devices and coaching support—that has the potential to address this problem. This is a protocol to assess the feasibility of OnTrack for evaluation in a randomised control trial.

Methods and analysis

A mixed-method, single-arm study design will be used to evaluate the feasibility of OnTrack for hospital and community use. A minimum sample of 12 participants from a stroke unit will be involved in the study for 14 weeks. During week 1, 8 and 14 participants will complete assessments relating to their arm function, arm impairment and activation. During weeks 2–13, participants will use OnTrack to track their arm movement in real time, receive motivational messages and face-to-face sessions to address problems, gain feedback on activity and receive self-management skills coaching. All equipment will be loaned to study participants. A parallel process evaluation will be conducted to assess the intervention’s fidelity, dose and reach, using a mixed-method approach. A public and patient involvement group will oversee the study and help with interpretation and dissemination of qualitative and quantitative data findings.

Ethics and dissemination

Ethical approval granted by the National Health Service Health Research Authority, Health and Care Research Wales, and the London—Surrey Research Ethics Committee (ref. 19/LO/0881). Trial results will be submitted for publication in peer review journals, presented at international conferences and disseminated among stroke communities. The results of this trial will inform development of a definitive trial.

Trial registration number

NCT03944486.

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<![CDATA[Efficacy and economic evaluation of delivery of care with tele-continuous EEG in critically ill patients: a multicentre, randomised controlled trial (Tele-cRCT) study protocol]]> https://www.researchpad.co/article/N90f7250c-7134-4857-a106-dff918ba7bc0

Introduction

Some critically ill patients are confirmed by continuous electroencephalography (cEEG) monitoring that non-convulsive seizure (NCS) and/or non-convulsive status epilepticus (NCSE) are causes of their depressed level of consciousness. Shortage of epilepsy specialists, especially in developing countries, is a major limiting factor in implementing cEEG in general practice. Delivery of care with tele-continous EEG (tele-cEEG) may be a potential solution as this allows specialists from a central facility to remotely assist local neurologists from distant areas in interpreting EEG findings and suggest proper treatment. No tele-cEEG programme has been implemented to help improve quality of care. Therefore, this study is conducted to assess the efficacy and cost utility of implementing tele-cEEG in critical care.

Methods and analysis

The Tele-cRCT study is a 3-year prospective, randomised, controlled, parallel, multicentre, superiority trial comparing delivery of care through ‘Tele-cEEG’ intervention with ‘Tele-routine EEG (Tele-rEEG)’ in patients with clinical suspicion of NCS/NCSE. A group of EEG specialists and a tele-EEG system were set up to remotely interpret EEG findings in six regional government hospitals across Thailand. The primary outcomes are functional neurological outcome (modified Rankin Scale, mRS), mortality rate and incidence of seizures. The secondary outcomes are cost utility, length of stay, emergency visit/readmission, impact on changing medical decisions and health professionals’ perceptions about tele-cEEG implementation. Functional outcome (mRS) will be assessed at 3 and 7 days after recruitment, and again at time of hospital discharge, and at 90 days, 6 months, 9 months and 1 year. Costs and health-related quality of life will be assessed using the Thai version of the EuroQol-five dimensions-five levels (EQ-5D-5L) at hospital discharge, and at 90 days, 6 months, 9 months and 1 year.

Ethics and dissemination

This study has been approved by the ethics committees of the Faculty of Medicine, Chulalongkorn University, and of Ramathibodi Hospital, Mahidol University, and registered on Thai Clinical Trials Registry. The results will be disseminated in a peer-reviewed journal.

Trial registration number

TCTR20181022002; preresults.

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<![CDATA[Internet-delivered attentional bias modification training (iABMT) for the management of chronic musculoskeletal pain: a protocol for a randomised controlled trial]]> https://www.researchpad.co/article/N15f91de7-75b6-4d42-832f-2b51c88a73ed

Introduction

Chronic musculoskeletal pain is a complex medical condition that can significantly impact quality of life. Patients with chronic pain demonstrate attentional biases towards pain-related information. The therapeutic benefits of modifying attentional biases by implicitly training attention away from pain-related information towards neutral information have been supported in a small number of published studies. Limited research however has explored the efficacy of modifying pain-related biases via the internet. This protocol describes a randomised, double-blind, internet-delivered attentional bias modification intervention, aimed to evaluate the efficacy of the intervention on reducing pain interference. Secondary outcomes are pain intensity, state and trait anxiety, depression, pain-related fear, and sleep impairment. This study will also explore the effects of training intensity on these outcomes, along with participants’ perceptions about the therapy.

Methods and analysis

The study is a double-blind, randomised controlled trial with four arms exploring the efficacy of online attentional bias modification training versus placebo training theorised to offer no specific therapeutic benefit. Participants with chronic musculoskeletal pain will be randomised to one of four groups: (1) 10-session attentional modification group; (2) 10-session placebo training group; (3) 18-session attentional modification group; or (4) 18-session placebo training group. In the attentional modification groups, the probe-classification version of the visual-probe task will be used to implicitly train attention away from threatening information towards neutral information. Following the intervention, participants will complete a short interview exploring their perceptions about the online training. In addition, a subgroup analysis for participants aged 16–24 and 25–60 will be undertaken.

Ethics and dissemination

This study has been approved by the University of Southampton Research Ethics Committee. Results will be published in peer-reviewed journals, academic conferences, and in lay reports for pain charities and patient support groups.

Trial registration number

NCT02232100; Pre-results.

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<![CDATA[Rationale and design for studying organisation of care for intra-arterial thrombectomy in the Netherlands: simulation modelling study]]> https://www.researchpad.co/article/Nee7c705b-1a19-474b-a0a2-fbca2e19d2cb

Introduction

The introduction of intra-arterial thrombectomy (IAT) challenges acute stroke care organisations to provide fast access to acute stroke therapies. Parameters of pathway performance include distances to primary and comprehensive stroke centres (CSCs), time to treatment and availability of ambulance services. Further expansion of IAT centres may increase treatment rates yet could affect efficient use of resources and quality of care due to lower treatment volume. The aim was to study the organisation of care and patient logistics of IAT for patients with ischaemic stroke in the Netherlands.

Methods and analyses

Using a simulation modelling approach, we will quantify performance of 16 primary and CSCs offering IAT in the Netherlands. Patient data concerning both prehospital and intrahospital pathway logistics will be collected and used as input for model validation. A previously validated simulation model for intravenous thrombolysis (IVT) patients will be expanded with data of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry and trials performed in the Collaboration for New Treatments in Acute Stroke consortium to represent patient logistics, time delays and outcomes in IAT patients. Simulation experiments aim to assess effectiveness and efficiency of alternative network topologies, that is, IAT with or without IVT at the nearest primary stroke centre (PSC) versus centralised care at a CSC. Primary outcomes are IAT treatment rates and clinical outcome according to the modified Rankin Scale. Secondary outcomes include onset-to-treatment time and resource use. Mann-Whitney U and Fisher’s exact tests will be used to estimate differences for continuous and categorical variables. Model and parameter uncertainty will be tested using sensitivity analyses.

Ethics and dissemination

This will be the first study to examine the organisation of acute stroke care for IAT delivery on a national scale using discrete event simulation. There are no ethics or safety concerns regarding the dissemination of information, which includes publication in peer-reviewed journals and (inter)national conference presentations.

Trial registration number

ISRCTN99503308, ISRCTN76741621, ISRCTN19922220, ISRCTN80619088, NCT03608423; Pre-results.

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<![CDATA[Intermittent theta burst stimulation applied during early rehabilitation after stroke: study protocol for a randomised controlled trial]]> https://www.researchpad.co/article/N5cb58bf6-3bf8-43ad-9329-2ca293bf7ba0

Introduction

Intermittent theta burst stimulation (iTBS) applied to primary motor cortex (M1) has been shown to modulate both the excitability and connectivity of the motor system. A recent proof-of-principle study, based on a small group of hospitalised patients with acute ischemic stroke, suggested that iTBS applied to the ipsilesional M1 combined with physical therapy early after stroke can amplify motor recovery with lasting after effects. A randomised controlled clinical trial using a double-blind design is warranted to justify the implementation of iTBS-assisted motor rehabilitation in neurorehabilitation from an acute ischaemic stroke.

Methods/design

We investigate the effects of daily iTBS on early motor rehabilitation after stroke in an investigator-initiated, longitudinal randomised controlled trial. Patients (n=150) with hemiparesis receive either iTBS (600 pulses) applied to the ipsilesional motor cortex (M1) or a control stimulation (ie, coil placement over the parieto-occipital vertex in parallel to the interhemispheric fissure and with a tilt of 45°). On 8 consecutive workdays, a 45 min arm-centred motor training follows the intervention . The relative grip strength, defined as the grip force ratios of the affected and unaffected hands, serves as the primary outcome parameter. Secondary outcome parameters are measures of arm function (Action Research Arm Test, Fugl-Meyer Motor Scale), stroke severity (National Institutes of Health Stroke Scale), stroke-induced disability (modified Rankin Scale, Barthel Index), duration of inpatient rehabilitation, quality of life (EuroQol 5D), motor evoked potentials and the resting motor threshold of the ipsilesional M1.

Ethics and dissemination

The study was approved by the Ethics Commission of the Medical Faculty, University of Cologne, Germany (reference number 15-343). Data will be disseminated through peer-reviewed publications and presentations at conferences. Study title: Theta-Burst Stimulation in Early Rehabilitation after Stroke (acronym: TheSiReS). Study registration at German Registry for Clinical Trials (DRKS00008963) and at ClinicalTrials.gov (NCT02910024).

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<![CDATA[Midlife socioeconomic position and old-age dementia mortality: a large prospective register-based study from Finland]]> https://www.researchpad.co/article/N978ba4b8-87cd-4d24-9b66-14a8c808ede1

Objectives

To assess the association between multiple indicators of socioeconomic position and dementia-related death, and to estimate the contribution of dementia to socioeconomic differences in overall mortality at older ages.

Design

Prospective population-based register study.

Setting

Finland.

Participants

11% random sample of the population aged 70–87 years resident in Finland at the end of year 2000 (n=54 964).

Main outcome measure

Incidence rates, Kaplan-Meier survival probabilities and Cox regression HRs of dementia mortality in 2001–2016 by midlife education, occupational social class and household income measured at ages 53–57 years.

Results

During the 528 387 person-years at risk, 11 395 individuals died from dementia (215.7 per 10 000 person-years). Lower midlife education, occupational social class and household income were associated with higher dementia mortality, and the differences persisted to the oldest old ages. Compared with mortality from all other causes, however, the socioeconomic differences emerged later. Dementia accounted for 28% of the difference between low and high education groups in overall mortality at age 70+ years, and for 21% of the difference between lowest and highest household income quintiles. All indicators of socioeconomic position were independently associated with dementia mortality, low household income being the strongest independent predictor (HR=1.24, 95% CI 1.16 to 1.32), followed by basic education (HR=1.14, 1.06 to 1.23). Manual occupational social class was related to a 6% higher hazard (HR=1.06, 1.01 to 1.11) compared with non-manual social class. Adjustment for midlife economic activity, baseline marital status and chronic health conditions attenuated the excess hazard of low midlife household income, although significant effects remained.

Conclusion

Several indicators of socioeconomic position predict dementia mortality independently and socioeconomic inequalities persist into the oldest old ages. The results demonstrate that dementia is among the most important contributors to socioeconomic inequalities in overall mortality at older ages.

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<![CDATA[First clinical postmarketing experiences in the treatment of epilepsies with brivaracetam: a retrospective observational multicentre study]]> https://www.researchpad.co/article/Nbc1301a4-8a8b-4fbb-987f-834be5afaebf

Objectives

Brivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting.

Design

Retrospective, observational multicentre study.

Setting

We retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist.

Participants

Data of 615 epilepsy patients treated with BRV were included in the study.

Primary and secondary outcome measures

Efficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed.

Results

Overall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV.

Conclusions

The present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

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<![CDATA[Weaning from mechanical ventilation in people with neuromuscular disease: protocol for a systematic review]]> https://www.researchpad.co/article/N0cc79cd7-1b4e-44d0-bea3-eb19e6285070

Introduction

Neuromuscular diseases (NMD) are characterised by progressive muscular impairment. The muscle weakness is directly related to respiratory muscles weakness, causing reduction in vital capacity, especially when associated with mechanical ventilation (MV). Conventional MV weaning in NMD is generally difficult. Weaning process can be conducted in protocols such as: ‘T’ piece or Pressure Support Ventilaton. Weaning failure is frequent because of muscle weakness. Protocol aim is to assess the effects of different weaning protocols in NMD patients receiving invasive MV in weaning success rate, duration of weaning, intensive care unit (ICU) stay, hospital stay and ICU mortality.

Methods and analysis

A search will be carried in the Cochrane Neuromuscular Specialised Register, MEDLINE, EMBASE, Web of Science, Scopus, United States National Institutes of Health Clinical Trials Registry, ClinicalTrials.gov and WHO International Clinical Trial Registry Protal, of randomised controlled trials (RCTs) and quasi-RCTs. Inclusion criteria of individuals are adults (above 16 years old) and children (from 5 to 16 years old), with clinical diagnosis of NMD (muscular dystrophy, amyotrophic lateral sclerosis, congenital myasthenia, myasthenia gravis, congenital myopathy, spinal muscular atrophy, Guillian Barré Syndrome, severe inherited neuropathies, metabolic myopathies, inflammatory myopathies, mitochondrial diseases) of any gender. All patients ventilated for at least 48 hours due to respiratory failure and clinically considered ready for weaning. Other respiratory or cardiovascular diagnosis associated will not be included. Intervention assessed will be weaning from MV using a protocol with 30 min to 2 hours of spontaneous breathing trial at the end point. All comparisons of different protocols will be considered.

Ethics and dissemination

Formal ethical approval is not required as primary data will not be collected, since it will be a systematic review. All studies included should have ethical committee approval. The results will be disseminated through a peer-reviewed publication and in conferences and congresses or symposia.

PROSPERO registration number

CRD42019117393.

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<![CDATA[Benefit of carotid revascularisation for women with symptomatic carotid stenosis: protocol for a systematic review]]> https://www.researchpad.co/article/N4c22e3b5-e630-4fcb-854a-3a01ad7162be

Introduction

Carotid intervention in the form of endarterectomy or stenting is the current standard of care for the majority of patients with symptomatic high-grade carotid stenosis. However, some randomised controlled trials (RCT) have demonstrated that women benefited significantly less from intervention than men. It is unclear if this is a true phenomenon or a study sampling artefact, as women were severely under-represented in all RCTs of carotid revascularisation. A systematic review is needed to summarise the existing data and to answer the question of whether a women-only trial for symptomatic patients with ipsilateral carotid stenosis is scientifically necessary and ethically permissible.

Methods and analysis

We will systematically search Medline, Embase, PubMed and the Cochrane libraries for all studies with data from RCTs that included women and compared either endarterectomy with stenting or revascularisation (by means of endarterectomy or stenting) with medical therapy in patients with symptomatic carotid stenosis. Search dates will be restricted to 1991–2018. Two reviewers will conduct screening search results, study selection, data extraction and quality assessment. We will include all studies reporting outcomes of interest. Planned subgroup analysis based on revascularisation technique, degree of stenosis and timing of intervention from the index event will be conducted with enough data.

Ethics and dissemination

This research is exempt of ethics approval as no primary data will be collected. The results will be published in peer-reviewed journals and disseminated through national and international-level conferences and scientific meetings. The result of this comprehensive review will provide useful information on whether further RCTs are required to study a women-only population with symptomatic carotid disease.

PROSPERO registration number

CRD42019134967.

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<![CDATA[Hospital-based cohort study to determine the association between home-time and disability after stroke by age, sex, stroke type and study year in Canada]]> https://www.researchpad.co/article/N62dba611-6a9d-4ae7-a747-e8d29ff3b248

Objective

Home-time is an emerging patient-centred stroke outcome metric, but it is not well described in the population. We aimed to determine the association between 90-day home-time and global disability after stroke. We hypothesised that longer home-time would be associated with less disability.

Design

Hospital-based cohort study of patients with ischaemic stroke or intracerebral haemorrhage admitted to an acute care hospital between 1 April 2002 and 31 March 2013.

Setting

All regional stroke centres and a simple random sample of patients from all other hospitals across the province of Ontario, Canada.

Participants

We included 39 417 adult patients (84% ischaemic, 16% haemorrhage), 53% male, with a median age of 74 years. We excluded non-residents of Ontario, patients without a valid health insurance number, patients discharged against medical advice or those who failed to return from a pass, patients living in a long-term care centre at baseline and stroke events occurring in-hospital.

Primary outcome measure

Association between 90-day home-time, defined as the number of days spent at home in the first 90 days after stroke, obtained using linked administrative data and modified Rankin Scale score at discharge.

Results

Compared with people with no disability, those with minimal disability had less home-time (adjusted rate ratio (aRR) 0.96, 95% CI 0.93 to 0.98) and those with the most severe disability had the least home-time (aRR 0.05, 95% CI 0.04 to 0.05). We found no clinically relevant modification by stroke type, sex or study year. However, for a given level of disability, older patients experienced less home-time compared with younger patients.

Conclusions

Our results provide content validity for home-time to be used to monitor stroke outcomes in large populations or to study temporal trends. Older patients experience less home-time for a given level of disability, suggesting the need for stratification by age.

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<![CDATA[Comorbidity in adults with traumatic brain injury and all-cause mortality: a systematic review]]> https://www.researchpad.co/article/Nfe38e1e9-4f25-42b2-9bcb-e93a02dd5aef

Objectives

Comorbidity in traumatic brain injury (TBI) has been recognised to alter the clinical course of patients and influence short-term and long-term outcomes. We synthesised the evidence on the effects of different comorbid conditions on early and late mortality post-TBI in order to (1) examine the relationship between comorbid condition(s) and all-cause mortality in TBI and (2) determine the influence of sociodemographic and clinical characteristics of patients with a TBI at baseline on all-cause mortality.

Design

Systematic review.

Data sources

Medline, Central, Embase, PsycINFO and bibliographies of identified articles were searched from May 1997 to January 2019.

Eligibility criteria for selecting studies

Included studies met the following criteria: (1) focused on comorbidity as it related to our outcome of interest in adults (ie, ≥18 years of age) diagnosed with a TBI; (2) comorbidity was detected by any means excluding self-report; (3) reported the proportion of participants without comorbidity and (4) followed participants for any period of time.

Data extraction and synthesis

Two independent reviewers extracted the data and assessed risk of bias using the Quality in Prognosis Studies tool. Data were synthesised through tabulation and qualitative description.

Results

A total of 27 cohort studies were included. Among the wide range of individual comorbid conditions studied, only low blood pressure was a consistent predictors of post-TBI mortality. Other consistent predictors were traditional sociodemographic risk factors. Higher comorbidity scale, scores and the number of comorbid conditions were not consistently associated with post-TBI mortality.

Conclusions

Given the high number of comorbid conditions that were examined by the single studies, research is required to further substantiate the evidence and address conflicting findings. Finally, an enhanced set of comorbidity measures that are suited for the TBI population will allow for better risk stratification to guide TBI management and treatment.

PROSPERO registration number

CRD42017070033

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<![CDATA[Correlation between biomarkers of pain in saliva and PAINAD scale in elderly people with cognitive impairment and inability to communicate: descriptive study protocol]]> https://www.researchpad.co/article/N8bee9608-e949-4d70-82ce-2154ae25c703

Introduction

Pain is an under-diagnosed problem in elderly people, especially in those with cognitive impairment who are unable to verbalise their pain. Although the Pain assessment in advanced dementia scale (PAINAD) scale is a tool recognised for its clinical interest in this type of patients, its correlation with the saliva biomarkers reinforced its utility. The aim of this research will be to correlate the scores of this scale with the levels of biomarkers of pain found in saliva samples of patients with cognitive impairment and inability to communicate.

Methods and analysis

This is an observational study. The level of pain will be evaluated using the PAINAD scale. Moreover, pain biomarkers, in particular secretory IgA and soluble tumour necrosis factor receptor type II, will be determined in saliva. Both assessments will be conducted in 75 patients aged over 65 years with advanced cognitive impairment and inability to communicate. The PAINAD scores will be correlated with the levels of these biomarkers of pain. A control group consisting of 75 healthy subjects aged over 65 years will be included in the study. Moreover, sociodemographic variables and variables related to pain, dementia and other clinical conditions will be recorded. The analysis will be performed with the statistical package SPSS V.22 and the software R.

Ethics and dissemination

The study has been reviewed and approved by the Andalusian Human Research Ethics Committee. In addition, this study has been financed by the Junta de Andalucía through a regional health research fund (Research code: PI-0357–2017). The results will be actively disseminated trough a high-impact journal in our study area, conference presentations and social media.

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<![CDATA[Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial]]> https://www.researchpad.co/article/N84badc19-b4ae-4998-8181-6a537b3c0535

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no known cure and with an average life expectancy of 3–5 years post diagnosis. The use of complementary medicine such as medicinal cannabis in search for a potential treatment or cure is common in ALS. Preclinical studies have demonstrated the efficacy of cannabinoids in extending the survival and slowing of disease progression in animal models with ALS. There are anecdotal reports of cannabis slowing disease progression in persons with ALS (pALS) and that cannabis alleviated the symptoms of spasticity and pain. However, a clinical trial in pALS with these objectives has not been conducted.

Methods and analysis

The Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease trial is a randomised, double-blind, placebo-controlled cannabis trial in pALS conducted at the Gold Coast University Hospital, Australia. The investigational product will be a cannabis-based medicine extract (CBME) supplied by CannTrust Inc., Canada, with a high-cannabidiol-low-tetrahydrocannabinol concentration. A total of 30 pALS with probable or definite ALS diagnosis based on the El Escorial criteria, with a symptom duration of <2 years, age between 25 and 75

years and with at least 70% forced vital capacity (FVC) will be treated for 6 months. The primary objective of the study is to evaluate the efficacy of CBME compared with placebo in slowing the disease progression measured by differences in mean ALS Functional Rating Scale-Revised and FVC score between the groups at the end of treatment. The secondary objectives are to evaluate the safety and tolerability of CBME by summarising adverse events, the effects of CBME on spasticity, pain, weight loss and quality of life assessed by the differences in mean Numeric Rating Scale for spasticity and Numeric Rating Scale for pain, percentage of total weight loss and ALS specific quality of life-Revised questionnaire.

Ethics and dissemination

The study has been approved by the local Institutional Review Board. The results of this study will be published in a peer-reviewed journal.

Trial registration number

NCT03690791

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<![CDATA[Playing board games, cognitive decline and dementia: a French population-based cohort study]]> https://www.researchpad.co/article/5acd8299463d7e2673e17c98

Objectives

To study the relationship between board game playing and risk of subsequent dementia in the Paquid cohort.

Design

A prospective population-based study.

Setting

In the Bordeaux area in South Western France.

Participants

3675 non-demented participants at baseline.

Primary outcome measure

The risk of dementia during the 20 years of follow-up.

Results

Among 3675 non-demented participants at baseline, 32.2% reported regular board game playing. Eight-hundred and forty participants developed dementia during the 20 years of follow-up. The risk of dementia was 15% lower in board game players than in non-players (HR=0.85, 95% CI 0.74 to 0.99; p=0.04) after adjustment on age, gender, education and other confounders. The statistical significance disappeared after supplementary adjustment on baseline mini-mental state examination (MMSE) and depression (HR=0.96, 95% CI 0.82 to 1.12; p=0.61). However, board game players had less decline in their MMSE score during the follow-up of the cohort (β=0.011, p=0.03) and less incident depression than non-players (HR=0.84; 95% CI 0.72 to 0.98; p<0.03).

Conclusions

A possible beneficial effect of board game playing on the risk of dementia could be mediated by less cognitive decline and less depression in elderly board game players.

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<![CDATA[Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis]]> https://www.researchpad.co/article/5b447e7e463d7e3ca3cae934

Objectives

Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding.

Design and setting

Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers.

Participants

29 cohort studies including 5100 infants/children.

Interventions

Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group.

Primary and secondary outcome measures

Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes.

Results

The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control.

Conclusions

Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen.

Trial registration number

PROSPERO database (CRD42014008925).

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<![CDATA[Protocol for a prospective interventional trial to develop a diagnostic index test for stroke as a cause of vertigo, dizziness and imbalance in the emergency room (EMVERT study)]]> https://www.researchpad.co/article/5b44979f463d7e3e2b4383c9

Introduction

Identifying stroke as a cause of acute vertigo, dizziness and imbalance in the emergency room is still a clinical challenge. Many patients are admitted to stroke units, but only a minority will have strokes. This imposes a heavy financial burden on the healthcare system. The aim of this study is to develop a diagnostic index test to identify patients with a high risk of having a stroke as the cause of acute vertigo and imbalance.

Methods and analysis

Patients with acute onset of vertigo, dizziness, postural imbalance or double vision within the last 24 hours lasting for at least 10 min are eligible to be included in the study. Patients with clinically proven peripheral or central aetiology will be excluded. In the emergency room, all enrolled patients will undergo standardised neuro-ophthalmological/physiological testing (including video-oculography, mobile posturography, measurement of subjective visual vertical) (EMVERT block 1). Within 10 days, standardised MRI will be performed as a reference test to identify stroke (EMVERT block 2). Data from EMVERT block 2 will be compared with results from block 1 in order to devise a diagnostic index test with a high specificity and sensitivity to predict the risk of stroke in the emergency room.

Ethics and dissemination

The study was approved by the ethics committee of the University of Munich and will be conducted according to the Guideline for Good Clinical Practice, the Federal Data Protecting Act and the Helsinki Declaration of the World Medical Association in its recent version. Study results are expected to be published in international peer-reviewed journals and will be presented at international conferences.

Trial registration number

German Clinical Trial Register: DRKS00008992; Universal trial number: U1111-1172-8719); pre-results.

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<![CDATA[Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project]]> https://www.researchpad.co/article/5b3b825b463d7e11c332c3a7

Objectives

To describe the prevalence of brain MRI incidental findings (IF) in a cohort of cognitively normal first-degree descendants of patients with Alzheimer's disease (AD).

Design

Cross-sectional observational study.

Setting

All scans were obtained with a 3.0 T scanner. Scans were evaluated by a single neuroradiologist and IF recorded and categorised. The presence of white matter hyperintensities (WMH) was determined with the Fazekas scale and reported as relevant if ≥2.

Participants

575 participants (45–75 years) underwent high-resolution structural brain MRI. Participants were cognitively normal and scored over the respective cut-off values in all the following neuropsychological tests: Mini-Mental State Examination (≥26), Memory Impairment Screen (≥6), Time Orientation Subtest of the Barcelona Test II (≥68), verbal semantic fluency (naming animals ≥12). Clinical Dementia Rating (CDR) had to be 0.

Results

155 participants (27.0%) presented with at least one IF. Relevant WMH were present in 7.8% of the participants, and vascular abnormalities, cyst and brain volume loss in 10.7%, 3.1% and 6.9% of the study volunteers, respectively. Neoplastic brain findings were found in 2.4% of participants and within these, meningiomas were the most common (1.7%) and more frequently found in women. A positive correlation between increasing age and the presence of IF was found. Additionally, brain atrophy greater than that expected by age was significantly more prevalent in participants without a parental history of AD.

Conclusions

Brain MRIs of healthy middle-aged participants show a relatively high prevalence of IF even when study participants have been screened for subtle cognitive alterations. Most of our participants are first-degree descendants of patients with AD, and therefore these results are of special relevance for novel imaging studies in the context of AD prevention in cognitively healthy middle-aged participants.

Trial registration number

NCT02198586.

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<![CDATA[Study rationale and protocol of the BARICO study: a longitudinal, prospective, observational study to evaluate the effects of weight loss on brain function and structure after bariatric surgery]]> https://www.researchpad.co/article/5c644658d5eed0c484c2bb4f

Introduction

Weight loss after bariatric surgery (BS) is often associated with improved cognition and structural brain recovery. However, improved cognition after BS is not always exhibited by patients, in fact, in some cases there is even a decline in cognition. Long-term consequences of BS weight loss, in terms of obesity and related diseases, can be hard to determine due to studies having short follow-up periods and small sample sizes.

The aim of the BARICO study (BAriatric surgery Rijnstate and Radboudumc neuroImaging and Cognition in Obesity) is to determine the long-term effect of weight loss after BS on brain function and structure, using sensitive neuropsychological tests and (functional) MRI ((f)MRI). Secondary study endpoints are associated with changes in metabolic and inflammation status of adipose tissue, liver and gut, in relation to brain structure and function. Also, the possible correlation between weight loss, gut microbiota composition change and neuropsychological outcomes will be investigated.

Methods and analysis

Data from 150 Dutch BS patients (ages between 35 and 55, men and women) will be collected at various time points between 2 months before and up to 10 years after surgery. Neuropsychological tests, questionnaires, blood, faeces and tissue samples will be collected before, during and after surgery to measure changes in cognition, microbiota, metabolic activity and inflammation over time. A subgroup of 75 participants will undergo (f)MRI in relation to executive functioning (determined by the Stroop task), grey and white matter volumes and cerebral blood flow. Regression analyses will be used to explore associations between weight loss and outcome measures.

Ethics and dissemination

This study has been approved by the medical review ethics committee CMO Region Arnhem and Nijmegen (NL63493.091.17). Research findings will be published in peer-reviewed journals and at conferences.

Trial registration number

NTR7288.

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