Conectar
Child maltreatment (CM) is a complex global public health issue with potentially devastating effects on individuals’ physical and mental health and well-being throughout the life course. A lack of uniform definitions hinders attempts to identify, measure, respond to, and prevent CM. The aim of this electronic Delphi (e-Delphi) study is to build consensus on definitions and types of CM for use in surveillance and multi-sectoral research in the 34 countries in the Euro-CAN (Multi-Sectoral Responses to Child Abuse and Neglect in Europe) project (COST Action CA19106).
The e-Delphi study will consist of a maximum of three rounds conducted using an online data collection platform. A multi-disciplinary expert panel consisting of researchers, child protection professionals (health and social care), police, legal professionals and adult survivors of CM will be purposefully recruited. We will approach approximately 100 experts, with between 50 and 60 of these anticipated to take part. Participants will rate their agreement with a range of statements relating to operational definitions and types of CM, and free-text comments on each of the statements to give further detail about their responses and areas of uncertainty. Consensus has been defined a priori as ≥70% of the panel agreeing or disagreeing with the statement after the final round. The responses to the open-ended questions will be analysed using a ‘codebook’ approach to thematic analysis, and used to refine the statements between rounds where no consensus is reached.
Ethical approval has been granted from the Cardiff University School of Medicine ethics committee (reference number SMREC22/96). Results will be submitted for publication in a peer-reviewed journal and presented at workshops (including for the participants) and international academic conferences. The Euro-CAN network will also be used to disseminate the results, with results briefings and presentations to key public health and other relevant organisations in the field.
Brief interventions that reduce suicide risk following youth’s experience with acute care due to suicidality are needed.
The study will use a three-arm randomised controlled trial designed to test the effectiveness of the Safety Planning Intervention with structured follow-up (SPI+) and the Collaborative Assessment and Management of Suicidality (CAMS) compared with enhanced usual care. The primary outcomes measure will be suicidal events, defined as death by suicide, attempted suicide, preparatory acts toward imminent suicidal behaviour or suicidal ideation resulting in a change in emergency evaluation or inpatient admission. Secondary measures will be the number of suicide attempts and severity of suicidal ideation. The experimental interventions, SPI+ and CAMS, consist of up to eight sessions over approximately 8 weeks that are designed to manage (SPI+) or treat (CAMS) patient-identified ‘drivers’ of suicidal thoughts and behaviours. Mechanisms and moderators of change will be evaluated to understand treatment impacts.
This study has been approved by the Seattle Children’s Institutional Review Board and is monitored by external agencies including the University of Washington Institute for Translational Health Sciences, and a National Institute of Mental Health (NIMH)-appointed Data Safety and Monitoring Board. Trial results will help establish evidence towards safe and effective treatment strategies for youth transitioning from acute to outpatient care due to a suicidal crisis. The data will be shared with the NIMH Data Archives and disseminated through publications and conferences.
by Pauline Rasset, Benoît Montalan, Jessica Mange
There is a great deal of indirect evidence suggesting that people with facial difference (FD) may be dehumanized. This research aimed to provide direct evidence of the dehumanization of people with FD based on the stigmatizing reactions they elicit. More precisely, previous findings revealed that the specific way people with FD are looked upon is related to the feelings of disgust they elicit. Since disgust fosters dehumanization, our aim was to confirm the modified pattern of visual attention towards people with FD and to determine whether it was also related to humanness perception. For that purpose, a preregistered eye-tracking study (N = 97) using a former experimental design extended to humanity attributions was conducted. This research replicates findings showing that the face of people with FD is explored differently in comparison with other human faces. However, the hypothesis that people with FD were given fewer humanity attributions was not supported. Therefore, the hypothesis of a "dehumanizing gaze" towards people with FD–beyond humanity-related attributions–is discussed in light of these findings.by Magdalena Blanz, Marie Balasse, Delphine Frémondeau, Erika Gál, Anett Osztás, Anna Zs. Biller, Éva Á. Nyerges, Denis Fiorillo, Eszter Bánffy, Maria Ivanova
The earliest introduction of livestock (cattle, goats, sheep, pigs) into the Carpathian Basin was an important step towards farming expansion into continental Europe. This spread beyond the environments of the southern Balkans was accompanied by a reduction in the spectrum of cultivated crops, changes in the relative representation of different domestic animals, and, most likely, adaptations of husbandry practices. How the earliest farmers in the Carpathian Basin kept their domestic stock is still understudied. We explored early animal management and land use strategies at the Starčevo settlement at Alsónyék-Bátaszék, Hungary (Early Neolithic, ca. 5800–5600 cal BC). Settled at the intersection of wide alluvial plains, waterlogged meadows and marshes to the east, and forested hills to the west, early farmers at Alsónyék had a wide variety of options for nourishing their livestock. We performed stable isotope ratio analysis of bone collagen (n = 99; δ13C, δ15N) and tooth enamel (nteeth = 28, sequentially sampled for δ13C and δ18O) from wild and domestic animals to locate them in the landscape and investigate herding practices on a seasonal scale. The bone collagen isotope ratios mostly indicate feeding in open environments. However, results from the sequential analysis of cattle and sheep enamel suggest diverse dietary strategies for winters, including consumption of forest resources, consumption of summer hay and grazing in an open environment. Most pigs appear to have had herbivorous diets, but several individuals likely supplemented their diet with animal protein. Stable isotope ratio results from the Lengyel phase at Alsónyék (ca. 4800–4300 cal BC) suggest more access to animal protein for pigs, and feeding in more open areas by wild boar, red deer and cattle compared to the Starčevo phase. This study’s results demonstrate considerable variability in early animal husbandry practices at Alsónyék.In Aotearoa New Zealand (NZ), integration across the healthcare continuum has been a key approach to strengthening the health system and improving health outcomes. A key example has been four regional District Health Board (DHB) groupings, which, from 2011 to 2022, required the country’s 20 DHBs to work together regionally. This research explores how this initiative functioned, examining how, for whom and in what circumstances regional DHB groupings worked to deliver improvements in system integration and health outcomes and equity.
We used a realist-informed evaluation study design. We used documentary analysis to develop programme logic models to describe the context, structure, capabilities, implementation activities and impact of each of the four regional groupings and then conducted interviews with stakeholders. We developed a generalised context-mechanisms-outcomes model, identifying key commonalities explaining how regional work ‘worked’ across NZ while noting important regional differences.
NZ’s four regional DHB groupings.
Forty-nine stakeholders from across the four regional groupings. These included regional DHB governance groups and coordinating regional agencies, DHB senior leadership, Māori and Pasifika leadership and lead clinicians for regional work streams.
Regional DHB working was layered on top of an already complex DHB environment. Organisational heterogeneity and tensions between local and regional priorities were key contextual factors. In response, regional DHB groupings leveraged a combination of ‘hard’ policy and planning processes, as well as ‘soft’, relationship-based mechanisms, aiming to improve system integration, population health outcomes and health equity.
The complexity of DHB regional working meant that success hinged on building relationships, leadership and trust, alongside robust planning and process mechanisms. As NZ reorients its health system towards a more centralised model underpinned by collaborations between local providers, our findings point to a need to align policy expectations and foster environments that support connection and collegiality across the health system.
Improving healthcare quality in low-/middle-income countries (LMICs) is a critical step in the pathway to Universal Health Coverage and health-related sustainable development goals. This study aimed to map the available evidence on the impacts of health system governance interventions on the quality of healthcare services in LMICs.
We conducted a scoping review of the literature. The search strategy used a combination of keywords and phrases relevant to health system governance, quality of healthcare and LMICs. Studies published in English until August 2023, with no start date limitation, were searched on PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, Google Scholar and ProQuest. Additional publications were identified by snowballing. The effects reported by the studies on processes of care and quality impacts were reviewed.
The findings from 201 primary studies were grouped under (1) leadership, (2) system design, (3) accountability and transparency, (4) financing, (5) private sector partnerships, (6) information and monitoring; (7) participation and engagement and (8) regulation.
We identified a stronger evidence base linking improved quality of care with health financing, private sector partnerships and community participation and engagement strategies. The evidence related to leadership, system design, information and monitoring, and accountability and transparency is limited.
Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care.
Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of –2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.
The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40–50 UK ICUs.
The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines.
ClinicalTrials.gov NCT03653832.
The Finnish Retirement and Aging (FIREA) Study was set up to study changes in health behavioural and cardiometabolic risk factors across retirement transition, and to examine the long-term consequences of work and retirement on health and functioning with advancing age.
Public sector workers whose estimated statutory retirement date was in 2014–2019 were invited to participate by sending them a questionnaire 18 months prior to their estimated retirement date. In the first phase of the FIREA Study, participants were followed up with annual surveys, accelerometer and clinical measurements during retirement transition into post-retirement years. The FIREA survey cohort includes 6783 participants, of which 908 belong also to the activity substudy and 290 to the clinical substudy.
Collected data include survey measures about health, lifestyle factors, psychosocial distress, work-related factors as well as retirement intentions. Accelerometer and GPS devices are used to measure 24-hour movement behaviours. Clinical examination includes blood and hair sample, measurements of anthropometry, cardiovascular function, physical fitness, physical and cognitive function. Our results suggest that in general retirement transition seems to have beneficial influence on health behaviours as well as on physical and mental health, but there are large individual differences, and certain behaviours such as sedentariness tend to increase especially among those retiring from manual occupations.
The second phase of the FIREA Study will be conducted during 2023–2025, when participants are 70 years old. The FIREA Study welcomes research collaboration proposals that fall within the general aims of the project.
To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome.
This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%.
Specialist outpatient services.
Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England.
A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England.
55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics.
This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.
Personal recovery is an important aspect for many individuals diagnosed with schizophrenia, as people can live rich, fulfilling lives despite ongoing symptoms. Prior reviews have found several factors to be associated with personal recovery, but a comprehensive overview of the psychosocial interventions aimed at improving personal recovery in schizophrenia is needed.
Key terms relating to personal recovery and psychosocial interventions to promote personal recovery will be searched for in the following databases: PubMed, EMBASE, PsycINFO, CINAHL, MEDLINE, Google Scholar, Web of Science Core Collection and Cochrane. Additionally, a simple search for grey literature will be conducted in The Networked Digital Library of Theses and Dissertations. Two reviewers will individually screen and extract the data, and the selection of sources will be documented in a Preferred Reporting Items for Systematic reviews and Meta-Analyses flow chart. A content analysis will be conducted on the data, and the findings will be presented in tables, and narratively synthesised. Lastly, research gaps will be identified, and recommendations for future research will be proposed.
Ethics approval was not required for the development or publishing of this protocol. Findings will be disseminated through conferences, meeting with patient organisations and consumers, and published in a peer-reviewed scientific journal.
Countries in the WHO’s African region have found community-based surveillance useful in ensuring the effectiveness of the Integrated Disease Surveillance and Response strategy. This approach encourages community participation in the surveillance system, in addition to early detection of outbreaks and other health threats. Thus, advancements in mobile health have the potential to improve community-based surveillance in Africa. The purpose of this review is to map evidence on available mhealth tools for community-based infectious disease surveillance in Africa.
The scoping review will follow a mixed-methods approach in line with the framework of Arksey and O’Malley amended by Levac and colleagues and the Joanna Briggs Institute. To retrieve published literature, PubMed, Scopus, Web of Science, Google Scholar and Google databases will be explored. Websites of organisations involved in surveillance activities across the African region will also be explored. Authors will be interested in published literature between 2000 and 2022 in any language. The primary investigator and a second author will independently review the retrieved titles according to the inclusion criteria, while a third reviewer will resolve conflicts that may arise. The review will map evidence according to the key concepts (mhealth, community-based surveillance and Africa) to inform stakeholders and mhealth designers on best practices to adopt involving mhealth approaches at the community level and mhealth tool designs, respectively. Results following the review will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: Extension for Scoping Review Guidelines.
Ethical approval is not required for scoping reviews as it does not involve the use of human subjects. This review is the first phase in an overall project on digital health. The findings of the review will be published in a peer-reviewed journal and disseminated at suitable forums and conferences.
by Michael Sciaudone, Renzo Carpena, Maritza Calderón, Patricia Sheen, Mirko Zimic, Jorge Coronel, Robert H. Gilman, Natalie M. Bowman
Tuberculosis remains one of the leading causes of death worldwide, especially in low- and middle-income countries. Tuberculosis treatment and control efforts are hindered by the difficulty in making the diagnosis, as currently available diagnostic tests are too slow, too expensive, or not sufficiently sensitive. Recombinase polymerase amplification (RPA) is a novel technique that allows for the amplification of DNA rapidly, at constant temperature, and with minimal expense. We calculated and compared the limit of detection, sensitivity, and specificity of two RPA-based assays for the diagnosis of pulmonary tuberculosis, using two sets of published primers. We also calculated and compared the assays’ limits of detection and compared their performance using two different DNA extraction methods prior to amplification (a commercially available DNA extraction kit vs. the chelex method). The RPA-lateral flow assay had a limit of detection of 5 fg/μL of DNA, a sensitivity of 53.2%, and a specificity of 93.3%, while the real time-RPA assay had a limit of detection of 25 fg/μL of DNA, a sensitivity of 85.1%, and a specificity of 93.3%. There was no difference in assay performance when DNA extraction was carried out using the commercial kit vs. the chelex method. The real-time RPA assay has adequate sensitivity and specificity for the diagnosis of pulmonary tuberculosis and could be a viable diagnostic tool in resource-limited settings, but the lateral flow assay did not perform as well, perhaps due to the fact we used stored sputum specimens from a biorepository. More work is needed to optimize the RPA-lateral flow assay, to get a more accurate estimate of its specificity and sensitivity using prospectively collected specimens, and to develop both assays into point-of-care tests that can be easily deployed in the field.by John Efromson, Giuliano Ferrero, Aurélien Bègue, Thomas Jedidiah Jenks Doman, Clay Dugo, Andi Barker, Veton Saliu, Paul Reamey, Kanghyun Kim, Mark Harfouche, Jeffrey A. Yoder
Normal development of the immune system is essential for overall health and disease resistance. Bony fish, such as the zebrafish (Danio rerio), possess all the major immune cell lineages as mammals and can be employed to model human host response to immune challenge. Zebrafish neutrophils, for example, are present in the transparent larvae as early as 48 hours post fertilization and have been examined in numerous infection and immunotoxicology reports. One significant advantage of the zebrafish model is the ability to affordably generate high numbers of individual larvae that can be arrayed in multi-well plates for high throughput genetic and chemical exposure screens. However, traditional workflows for imaging individual larvae have been limited to low-throughput studies using traditional microscopes and manual analyses. Using a newly developed, parallelized microscope, the Multi-Camera Array Microscope (MCAM™), we have optimized a rapid, high-resolution algorithmic method to count fluorescently labeled cells in zebrafish larvae in vivo. Using transgenic zebrafish larvae, in which neutrophils express EGFP, we captured 18 gigapixels of images across a full 96-well plate, in 75 seconds, and processed the resulting datastream, counting individual fluorescent neutrophils in all individual larvae in 5 minutes. This automation is facilitated by a machine learning segmentation algorithm that defines the most in-focus view of each larva in each well after which pixel intensity thresholding and blob detection are employed to locate and count fluorescent cells. We validated this method by comparing algorithmic neutrophil counts to manual counts in larvae subjected to changes in neutrophil numbers, demonstrating the utility of this approach for high-throughput genetic and chemical screens where a change in neutrophil number is an endpoint metric. Using the MCAM™ we have been able to, within minutes, acquire both enough data to create an automated algorithm and execute a biological experiment with statistical significance. Finally, we present this open-source software package which allows the user to train and evaluate a custom machine learning segmentation model and use it to localize zebrafish and analyze cell counts within the segmented region of interest. This software can be modified as needed for studies involving other zebrafish cell lineages using different transgenic reporter lines and can also be adapted for studies using other amenable model species.by Ronald McDowell, Liam Heaney, Thomas Brown, Brendan Bunting, Hassan Burhan, Rekha Chaudhuri, Paddy Dennison, Shoaib Faruqi, Robin Gore, David J. Jackson, Andrew Menzies-Gow, Thomas Pantin, Mitesh Patel, Paul Pfeffer, Salman Siddiqui, John Busby, on behalf of the UK Severe Asthma Registry
BackgroundThe Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown.
MethodsData was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed.
ResultsA one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p Conclusion
The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.
by Magdalena Grzonkowska, Mariusz Baumgart, Michał Kułakowski, Michał Szpinda
Detailed numerical data about the development of primary ossification centers in human fetuses may influence both better evaluation and early detection of skeletal dysplasias, which are associated with delayed development and mineralization of ossification centers. To the best of our knowledge, this is the first report in the medical literature to morphometrically analyze the primary ossification center of the squamous part of temporal bone in human fetuses based on computed tomography imaging. The present study offers a precise quantitative foundation for ossification of the squamous part of temporal bone that may contribute to enhanced prenatal care and improved outcomes for fetuses with inherited cranial defects and skeletodysplasias. The examinations were carried out on 37 human fetuses of both sexes (16 males and 21 females) aged 18–30 weeks of gestation, which had been preserved in 10% neutral formalin solution. Using CT, digital image analysis software, 3D reconstruction and statistical methods, the size of the primary ossification center of the squamous part of temporal bone was evaluated. With neither sex nor laterality differences, the best-fit growth patterns for the primary ossification center of the squamous part of temporal bone was modelled by the linear function: y = −0.7270 + 0.7682 × age ± 1.256 for its vertical diameter, and the four-degree polynomial functions: y = 5.434 + 0.000019 × (age)4 ± 1.617 for its sagittal diameter, y = −4.086 + 0.00029 × (age)4 ± 2.230 for its projection surface area and y = −25.213 + 0.0004 × (age)4 ± 3.563 for its volume. The CT-based numerical data and growth patterns of the primary ossification center of the squamous part of temporal bone may serve as age-specific normative intervals of relevance for gynecologists, obstetricians, pediatricians and radiologists during screening ultrasound scans of fetuses. Our findings for the growing primary ossification center of the squamous part of temporal bone may be conducive in daily clinical practice, while ultrasonically monitoring normal fetal growth and screening for inherited cranial faults and skeletodysplasias.by Linda J. Paul, Aaron C. Ericsson, Frank M. Andrews, Zachary McAdams, Michael L. Keowen, Michael P. St Blanc, Heidi E. Banse
Equine glandular gastric disease (EGGD) is a common disease among athletic horses that can negatively impact health and performance. The pathophysiology of this EGGD remains poorly understood. Previous studies using controlled populations of horses identified differences in the gastric glandular mucosal microbiome associated with disease. The objective of this study was to compare the gastric microbiome in horses with EGGD and those without across multiple barns and differing management practices. We hypothesized that alterations in the microbiome of the gastric glandular mucosa are associated with EGGD. A secondary objective was to perform a risk factor analysis for EGGD using the diet and management data collected. Microbial populations of biopsies from normal pyloric mucosa of horses without EGGD (control biopsies), normal pyloric mucosa of horses with EGGD (normal biopsies) and areas of glandular mucosal disruption in horses with EGGD (lesion biopsies) were compared. Lesion biopsies had a different microbial community structure than control biopsies. Control biopsies had a higher read count for the phylum Actinomycetota compared to lesion biopsies. Control biopsies also had an enrichment of the genera Staphylococcus and Lawsonella and the species Streptococcus salivarius. Lesion biopsies had an enrichment of the genera Lactobacillus and Actinobacillus and the species Lactobacillus equigenerosi. These results demonstrate differences in the gastric glandular microbiome between sites of disrupted mucosa in horses with EGGD compared to pyloric mucosa of horses without EGGD. Risk factor analysis indicated that exercise duration per week was a risk factor for EGGD.by Kenneth S. Noguchi, Kevin Moncion, Elise Wiley, Ashley Morgan, Eric Huynh, Marla K. Beauchamp, Stuart M. Phillips, Lehana Thabane, Ada Tang
BackgroundStroke impacts nearly 14 million people annually. Muscle strength and physical function are often affected by stroke and important determinants of stroke recovery. Resistance exercise training (RT) has been shown to improve muscle strength, but RT prescriptions may be suboptimal for other aspects of stroke recovery. Parameters such as frequency, intensity, type, and duration may influence the effectiveness of RT interventions but have not been systematically evaluated.
Objectives1) To determine the effects of RT on stroke recovery, and 2) to examine the influence of RT parameters on intervention effects.
Eligibility criteriaRandomized controlled trials examining the effects of RT will be eligible for this systematic review if they: 1) included only adults with stroke or transient ischemic attack, 2) compared RT to no exercise or usual care, and 3) did not apply a co-intervention.
Study selectionEight databases (MEDLINE, EMBASE, EMCARE, AMED, PsychINFO, CINAHL, SPORTDiscus, and Web of Science) and 2 clinical trials registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) will be searched from inception. Two independent pairs of authors will compare titles, abstracts, and full-text reports against the eligibility criteria. Conflicts will be resolved by consensus or third author.
Main outcome measuresThe construct of interest is stroke recovery. An advisory group of clinicians, researchers, and partners with lived experience of stroke will be consulted to determine specific outcome measures of interest, and to rank their relative importance. We expect to include measures of physical function, strength, cognition, and quality of life. Random-effects meta-analyses will be used to pool results for each outcome across studies, and RT parameters (frequency, intensity, type, and duration) will be used as covariates in meta-regression analyses.
ConclusionThe results of this review will inform the optimal RT prescription parameters for promoting stroke recovery.
The Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial found that a group-based educational intervention to support people using strong opioids for chronic non-malignant pain helped a significant proportion of people to stop or decrease opioid use with no increase in pain-related disability. We report a linked process evaluation of the group-based intervention evaluated in comparison to a usual-care control group that received a self-help booklet and relaxation CD.
We interviewed 18 intervention facilitators, and 20 intervention and 20 control participants who had chronic non-malignant pain and were recruited from general (family) practices in the UK. Quantitative data included change mechanism questions on the trial questionnaires which explored motivation, expectations and self-efficacy. Fidelity was assessed by listening to a sample of audio-recorded group sessions and nurse consultations. Quantitative and qualitative data were integrated using ‘follow a thread’ and a mixed-methods matrix.
Four overarching themes emerged: (1) the right time to taper, (2) the backdrop of a life with chronic pain, (3) needing support and (4) the benefits of being in a group. Delivery fidelity was good, adherence (83%) and competence (79%) across a range of intervention groups. Staff delivering the intervention found three typical responses to the intervention: resistance, open to trying and feeling it was not the right time. The group experience was important to those in the intervention arm. It provided people with a forum in which to learn about the current thinking about opioid usage and its effects. It also gave them examples of how feasible or personally relevant coming off opioids might be.
The process evaluation data showed that the I-WOTCH intervention was well delivered, well received and useful for most interviewees. Being ‘the right time’ to taper and having support throughout tapering, emerged as important factors within the context of living with chronic pain.
by Alexia Loste, Marc Clément, Sandrine Delbosc, Kevin Guedj, Jean Sénémaud, Anh-Thu Gaston, Marion Morvan, Guillaume Even, Grégory Gautier, Alexander Eggel, Michel Arock, Emanuele Procopio, Catherine Deschildre, Liliane Louedec, Jean-Baptiste Michel, Lydia Deschamps, Yves Castier, Raphaël Coscas, Jean-Marc Alsac, Pierre Launay, Giuseppina Caligiuri, Antonino Nicoletti, Marie Le Borgne
AimsIgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression.
Methods and resultsThrough histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression.
ConclusionsOur data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.
FreshRSS 