The role of the deep cervical extensor muscles in multi-directional isometric neck strength.

Clinical management of whiplash-associated disorders is challenging and often unsuccessful, with over a third of whiplash injuries progressing to chronic neck pain. Previous imaging studies have identified muscle fat infiltration, indicative of muscle weakness, in the deep cervical extensor muscles (multifidus and semispinalis cervicis). Yet, kinematic and muscle redundancy prevent the direct assessment of individual neck muscle strength, making it difficult to determine the role of these muscles in motor dysfunction. The purpose of this study was to determine the effects of deep cervical extensor muscle weakness on multi-directional neck strength and muscle activation patterns. Maximum isometric forces and associated muscle activation patterns were computed in 25 test directions using a 3-joint, 24-muscle musculoskeletal model of the head and neck. The computational approach accounts for differential torques about the upper and lower cervical spine. To facilitate clinical translation, the test directions were selected based on locations where resistance could realistically be applied to the head during clinical strength assessments. Simulation results reveal that the deep cervical extensor muscles are active and contribute to neck strength in directions with an extension component. Weakness of this muscle group leads to complex compensatory muscle activation patterns characterized primarily by increased activation of the superficial extensors and deep upper cervical flexors, and decreased activation of the deep upper cervical extensors. These results provide a biomechanistic explanation for movement dysfunction that can be used to develop targeted diagnostics and treatments for chronic neck pain in whiplash-associated disorders.

OrthoFusion: A Super-Resolution Algorithm to Fuse Orthogonal CT Volumes.

OrthoFusion, an intuitive super-resolution algorithm, is presented in this study to enhance the spatial resolution of clinical CT volumes. The efficacy of OrthoFusion is evaluated, relative to high-resolution CT volumes (ground truth), by assessing image volume and derived bone morphological similarity, as well as its performance in specific applications in 2D-3D registration tasks. Results demonstrate that OrthoFusion significantly reduced segmentation time, while improving structural similarity of bone images and relative accuracy of derived bone model geometries. Moreover, it proved beneficial in the context of biplane videoradiography, enhancing the similarity of digitally reconstructed radiographs to radiographic images and improving the accuracy of relative bony kinematics. OrthoFusion's simplicity, ease of implementation, and generalizability make it a valuable tool for researchers and clinicians seeking high spatial resolution from existing clinical CT data. This study opens new avenues for retrospectively utilizing clinical images for research and advanced clinical purposes, while reducing the need for additional scans, mitigating associated costs and radiation exposure.

What is known about the health effects of non-steroidal anti-inflammatory drug (NSAID) use in marathon and ultraendurance running: a scoping review.

This systematic scoping review aimed to understand the extent and scope of evidence on the health risks of non-steroidal anti-inflammatory drug (NSAID) use in marathon and ultraendurance running. NSAIDs are commonly consumed by runners to combat pain and inflammation; however, the health risks of consuming these drugs during marathon and ultrarunning events are currently not fully understood. Four databases (Cochrane Library, PubMed, MEDLINE and SPORTDiscus) were searched to identify articles focusing on running events of 26.2 miles or further, and they must have reported on the health risks of NSAID use. There was no restriction on the study design or the date of publication. Thirty studies were ultimately included: 4 randomised controlled trials, 1 cross-sectional study, 11 retrospective reviews, 4 case reports, 1 non-randomised control trial, and 9 prospective observational studies. The literature showed that potential health concerns of NSAID use could be split into five categories: electrolyte balance and hyponatraemia; acute kidney injury (AKI); gastrointestinal disturbances; oxidative stress, inflammation and muscle damage; other medical concerns. None of these sections had clear statistically significant links with NSAID use in ultraendurance running. However, potential links were shown, especially in AKI and electrolyte balance. This review suggests there is very limited evidence to show that NSAIDs have a negative impact on the health of ultrarunning athletes. Indications from a few non-randomised studies of a possible effect on kidney function need exploring with more high-quality research.

Primary care clinicians' perspectives on interacting with patients with gynaecological conditions: a systematic review.

BACKGROUND: Studies have found that women with gynaecological conditions and symptoms do not feel listened to by primary care clinicians. Less understood is whether primary care clinicians perceive that there are challenges around listening to and interacting with this patient group. AIM: This study aims to understand primary care clinicians' perspectives on the challenges of listening to and interacting with women patients with gynaecological conditions and symptoms. DESIGN & SETTING: Systematic review METHOD: We searched ASSIA, CINAHL, Embase, HMIC and MEDLINE from inception to July 2023. We also conducted forward and backward citation searches of included studies. Identified records were screened independently by two reviewers. Data-extraction was undertaken by one reviewer and checked by a second. Quality appraisal used the Wallace checklist. "Best-fit" framework synthesis was used to synthesise findings around themes which explore the challenges of patient-clinician interaction. RESULTS: We identified 25 relevant papers. Perceived challenges associated with listening to and interacting with patients with gynaecological conditions and symptoms were identified at four 'levels': Individual clinician factors; structural and organisational factors; community and external factors; and factors related to gynaecological conditions. Interpretive analysis identified specific challenges relating to socio-cultural factors affecting the consultation experience; the need for further education, training or guidance for clinicians; factors affecting referral decisions; and factors related to service structure and organisation. CONCLUSIONS: Primary care clinicians acknowledge that empathy, respect and attentive listening are important when interacting with women patients with gynaecological conditions and symptoms. However, these ideals are impeded by several factors.

Cervical facet capsular ligament mechanics: Estimations based on subject-specific anatomy and kinematics.

Background: To understand the facet capsular ligament's (FCL) role in cervical spine mechanics, the interactions between the FCL and other spinal components must be examined. One approach is to develop a subject-specific finite element (FE) model of the lower cervical spine, simulating the motion segments and their components' behaviors under physiological loading conditions. This approach can be particularly attractive when a patient's anatomical and kinematic data are available. Methods: We developed and demonstrated methodology to create 3D subject-specific models of the lower cervical spine, with a focus on facet capsular ligament biomechanics. Displacement-controlled boundary conditions were applied to the vertebrae using kinematics extracted from biplane videoradiography during planar head motions, including axial rotation, lateral bending, and flexion-extension. The FCL geometries were generated by fitting a surface over the estimated ligament-bone attachment regions. The fiber structure and material characteristics of the ligament tissue were extracted from available human cervical FCL data. The method was demonstrated by application to the cervical geometry and kinematics of a healthy 23-year-old female subject. Results: FCL strain within the resulting subject-specific model were subsequently compared to models with generic: (1) geometry, (2) kinematics, and (3) material properties to assess the effect of model specificity. Asymmetry in both the kinematics and the anatomy led to asymmetry in strain fields, highlighting the importance of patient-specific models. We also found that the calculated strain field was largely independent of constitutive model and driven by vertebrae morphology and motion, but the stress field showed more constitutive-equation-dependence, as would be expected given the highly constrained motion of cervical FCLs. Conclusions: The current study provides a methodology to create a subject-specific model of the cervical spine that can be used to investigate various clinical questions by coupling experimental kinematics with multiscale computational models.

Endogenous H3.3K27M derived peptide restricted to HLA-A∗02:01 is insufficient for immune-targeting in diffuse midline glioma.

Diffuse midline glioma (DMG) is a childhood brain tumor with an extremely poor prognosis. Chimeric antigen receptor (CAR) T cell therapy has recently demonstrated some success in DMG, but there may a need to target multiple tumor-specific targets to avoid antigen escape. We developed a second-generation CAR targeting an HLA-A∗02:01 restricted histone 3K27M epitope in DMG, the target of previous peptide vaccination and T cell receptor-mimics. These CAR T cells demonstrated specific, titratable, binding to cells pulsed with the H3.3K27M peptide. However, we were unable to observe scFv binding, CAR T cell activation, or cytotoxic function against H3.3K27M+ patient-derived models. Despite using sensitive immunopeptidomics, we could not detect the H3.3K27M26-35-HLA-A∗02:01 peptide on these patient-derived models. Interestingly, other non-mutated peptides from DMG were detected bound to HLA-A∗02:01 and other class I molecules, including a novel HLA-A3-restricted peptide encompassing the K27M mutation and overlapping with the H3 K27M26-35-HLA-A∗02:01 peptide. These results suggest that targeting the H3 K27M26-35 mutation in context of HLA-A∗02:01 may not be a feasible immunotherapy strategy because of its lack of presentation. These findings should inform future investigations and clinical trials in DMG.

PROTOCOL: Health and social care interventions in the 80 years old and over population: An evidence and gap map.

This is the protocol for a Campbell systematic review. The objectives are as follows: identify available systematic reviews and randomised controlled trials on interventions targeting health or social needs of the people aged over 80; identify qualitative studies relating to the experiences of people aged over 80 of interventions that target their health or social needs; identify areas where systematic reviews are needed; identify gaps in evidence where further primary research is needed; assess equity considerations (using the PROGRESS plus criteria) in available systematic reviews, randomised trials and qualitative studies of identified interventions; assess gaps and evidence related to health equity.

What are the effects of animals on the health and wellbeing of residents in care homes? A systematic review of the qualitative and quantitative evidence.

BACKGROUND: There is some evidence to suggest that animal-assisted interventions can have beneficial impact for residents in long-term care, but the focus of the evidence has largely been on behavioural and psychosocial measured outcomes. Animals, either as companion animals or in the form of pet/animal-assisted therapy, may provide benefits in the form of social contact, as well as opportunities for sensory experiences and meaningful engagement not picked up by outcome tools. This review aimed to create a state-of-knowledge synthesis, bringing together qualitative and quantitative findings, on the impact of animal-human interaction on care home residents and care home staff. METHODS: Fourteen databases were searched from inception to July 2020. Forward and backward citation chasing of included articles was conducted. Screening was undertaken independently by a team of reviewers. Thematic synthesis and meta-analysis were used to synthesise the qualitative and quantitative data. RESULTS: Thirty-four studies, published in 40 articles (20 qualitative and 20 quantitative) were included. Five themes relating to resident wellbeing were identified in the qualitative evidence synthesis. These were animals as 'living beings', reminiscence and storytelling, caring (as 'doing' and 'feeling'), respite (from loneliness, institutionalisation, and illness), and sensory engagement. A sixth theme related to staff perceptions and wellbeing, and a seventh to animal health and wellbeing. Maintaining identity was identified as an overarching theme. The majority of randomised trials had small sample sizes and were rated as low quality, mostly showing no evidence of beneficial effect. There was, however, limited evidence of a positive effect of pet/animal interaction on outcomes of loneliness, anxiety and depression, supporting the themes of respite and sensory engagement. CONCLUSIONS: The presence of animals can significantly impact the health and wellbeing of some care home residents. Residents had meaningful relationships with animals and derived pleasure and comfort from them. Interacting with animals offered residents a way to maintain a sense of self in the care homes, and with support, residents with dementia could also express their identities. Facilitating residents to interact with animals as part of person-centred care may also help residents to feel 'at home' in the care home. TRIAL REGISTRATION: PROSPERO registration no: CRD42017058201.

Human EGFRvIII chimeric antigen receptor T cells demonstrate favorable safety profile and curative responses in orthotopic glioblastoma.

Objectives: Glioblastoma is a highly aggressive and fatal brain malignancy, and effective targeted therapies are required. The combination of standard treatments including surgery, chemotherapy and radiotherapy is not curative. Chimeric antigen receptor (CAR) T cells are known to cross the blood-brain barrier, mediating antitumor responses. A tumor-expressed deletion mutant of the epidermal growth factor receptor (EGFRvIII) is a robust CAR T cell target in glioblastoma. Here, we show our de novo generated, high-affinity EGFRvIII-specific CAR; GCT02, demonstrating curative efficacy in human orthotopic glioblastoma models. Methods: The GCT02 binding epitope was predicted using Deep Mutational Scanning (DMS). GCT02 CAR T cell cytotoxicity was investigated in three glioblastoma models in vitro using the IncuCyte platform, and cytokine secretion with a cytometric bead array. GCT02 in vivo functionality was demonstrated in two NSG orthotopic glioblastoma models. The specificity profile was generated by measuring T cell degranulation in response to coculture with primary human healthy cells. Results: The GCT02 binding location was predicted to be located at a shared region of EGFR and EGFRvIII; however, the in vitro functionality remained exquisitely EGFRvIII specific. A single CAR T cell infusion generated curative responses in two orthotopic models of human glioblastoma in NSG mice. The safety analysis further validated the specificity of GCT02 for mutant-expressing cells. Conclusion: This study demonstrates the preclinical functionality of a highly specific CAR targeting EGFRvIII on human cells. This CAR could be an effective treatment for glioblastoma and warrants future clinical investigation.

Macrophages and Intervertebral Disc Degeneration.

The intervertebral disc (IVD) aids in motion and acts to absorb energy transmitted to the spine. With little inherent regenerative capacity, degeneration of the intervertebral disc results in intervertebral disc disease, which contributes to low back pain and significant disability in many individuals. Increasing evidence suggests that IVD degeneration is a disease of the whole joint that is associated with significant inflammation. Moreover, studies show elevated macrophage accumulation within the IVD with increasing levels of disease severity; however, we still need to understand the roles, be they causative or consequential, of macrophages during the degenerative process. In this narrative review, we discuss hallmarks of IVD degeneration, showcase evidence of macrophage involvement during disc degeneration, and explore burgeoning research aimed at understanding the molecular pathways regulating macrophage functions during intervertebral disc degeneration.

Expert searchers identified time, team, technology and tension as challenges when carrying out supplementary searches for systematic reviews: A thematic network analysis.

BACKGROUND: Systematic reviews require detailed planning of complex processes which can present logistical challenges. Understanding these logistical challenges can help with planning and execution of tasks OBJECTIVES: To describe the perspectives of expert searchers on the main logistical challenges when carrying out supplementary searches for systematic reviews, in particular, forward citation searching and web searching. METHODS: Qualitative interviews were undertaken with 15 experts on searching for studies for systematic reviews (e.g. information specialists) working in health and social care research settings. Interviews were undertaken by video-call between September 2020 and June 2021. Data analysis used thematic network analysis. RESULTS: We identified three logistical challenges of using forward citation searching and web searching which were organised under the global theme of 'tension': time, team and technology. Several subthemes were identified which supported the organising themes, including allocating time, justifying time and keeping to time; reviewer expectations and contact with review teams; and access to resources and reference management. CONCLUSION: Forward citation searching and web searching are logistically challenging search methods for a systematic review. An understanding of these challenges should encourage expert searchers and review teams to maintain open channels of communication, which should also facilitate improved working relationships.

New horizons for caring for people with dementia in hospital: the DEMENTIA CARE pointers for service change.

Approximately two-thirds of hospital admissions are older adults and almost half of these are likely to have some form of dementia. People with dementia are not only at an increased risk of adverse outcomes once admitted, but the unfamiliar environment and routinised practices of the wards and acute care can be particularly challenging for them, heightening their confusion, agitation and distress further impacting the ability to optimise their care. It is well established that a person-centred care approach helps alleviate some of the unfamiliar stress but how to embed this in the acute-care setting remains a challenge. In this article, we highlight the challenges that have been recognised in this area and put forward a set of evidence-based 'pointers for service change' to help organisations in the delivery of person-centred care. The DEMENTIA CARE pointers cover areas of: dementia awareness and understanding, education and training, modelling of person-centred care by clinical leaders, adapting the environment, teamwork (not being alone), taking the time to 'get to know', information sharing, access to necessary resources, communication, involving family (ask family), raising the profile of dementia care, and engaging volunteers. The pointers extend previous guidance, by recognising the importance of ward cultures that prioritise dementia care and institutional support that actively seeks to raise the profile of dementia care. The pointers provide a range of simple to more complex actions or areas for hospitals to help implement person-centred care approaches; however, embedding them within the organisational cultures of hospitals is the next challenge.

Systematic reviews of convalescent plasma in COVID-19 continue to be poorly conducted and reported: a systematic review.

OBJECTIVES: To suggest possible approaches to combatting the impact of the COVID-19 infodemic to prevent research waste in future health emergencies and in everyday research and practice. STUDY DESIGN AND SETTING: Systematic review. The Epistemonikos database was searched in June 2021 for systematic reviews on the effectiveness of convalescent plasma for COVID-19. Two reviewers independently screened the retrieved references with disagreements resolved by discussion. Data extraction was completed by one reviewer with a proportion checked by a second. We used the Assessment of Multiple Systematic Reviews to assess the quality of conduct and reporting of included reviews. RESULTS: Fifty one systematic reviews are included with 193 individual studies included within the systematic reviews. There was considerable duplication of effort; multiple reviews were conducted at the same time with inconsistencies in the evidence included. The reviews were of low methodological quality, poorly reported, and did not adhere to preferred reporting items for systematic reviews and meta-analysis guidance. CONCLUSION: Researchers need to conduct, appraise, interpret, and disseminate systematic reviews better. All in the research community (researchers, peer-reviewers, journal editors, funders, decision makers, clinicians, journalists, and the public) need to work together to facilitate the conduct of robust systematic reviews that are published and communicated in a timely manner, reducing research duplication and waste, increasing transparency and accessibility of all systematic reviews.

To go or not to go? Biological logic gating engineered T cells.

Genetically engineered T cells have been successfully used in the treatment of hematological malignancies, greatly increasing both progression-free and overall survival in patients. However, the outcomes of patients treated with Chimeric Antigen Receptor (CAR) T cells targeting solid tumors have been disappointing. There is an unmet clinical need for therapies which are specifically designed to overcome the challenges associated with solid tumors such as tumor heterogeneity and antigen escape. Genetic engineering employing the use of biological logic gating in T cells is an emerging and cutting-edge field that may address these issues. The advantages of logic gating include localized secretion of anti-tumor proteins into the tumor microenvironment, multi antigen targeting of tumors and a potential increase in safety when targeting tumor antigens which may not be exclusively tumor specific. In this review, we introduce the concept of biological logic gating and how this technology addresses some of the challenges of current CAR T treatment. We outline the types of logic gating circuits and finally discuss the application of this new technology to engineered T cells, in the treatment of cancer.

Characteristics, quality and volume of the first 5 months of the COVID-19 evidence synthesis infodemic: a meta-research study.

OBJECTIVE: The academic and scientific community has reacted at pace to gather evidence to help and inform about COVID-19. Concerns have been raised about the quality of this evidence. The aim of this review was to map the nature, scope and quality of evidence syntheses on COVID-19 and to explore the relationship between review quality and the extent of researcher, policy and media interest. DESIGN AND SETTING: A meta-research: systematic review of reviews. INFORMATION SOURCES: PubMed, Epistemonikos COVID-19 evidence, the Cochrane Library of Systematic Reviews, the Cochrane COVID-19 Study Register, EMBASE, CINAHL, Web of Science Core Collection and the WHO COVID-19 database, searched between 10 June 2020 and 15 June 2020. ELIGIBILITY CRITERIA: Any peer-reviewed article reported as a systematic review, rapid review, overview, meta-analysis or qualitative evidence synthesis in the title or abstract addressing a research question relating to COVID-19. Articles described as meta-analyses but not undertaken as part of a systematic or rapid review were excluded. STUDY SELECTION AND DATA EXTRACTION: Abstract and full text screening were undertaken by two independent reviewers. Descriptive information on review type, purpose, population, size, citation and attention metrics were extracted along with whether the review met the definition of a systematic review according to six key methodological criteria. For those meeting all criteria, additional data on methods and publication metrics were extracted. RISK OF BIAS: For articles meeting all six criteria required to meet the definition of a systematic review, AMSTAR-2 ((A MeaSurement Tool to Assess systematic Reviews, version 2.0) was used to assess the quality of the reported methods. RESULTS: 2334 articles were screened, resulting in 280 reviews being included: 232 systematic reviews, 46 rapid reviews and 2 overviews. Less than half reported undertaking critical appraisal and a third had no reproducible search strategy. There was considerable overlap in topics, with discordant findings. Eighty-eight of the 280 reviews met all six systematic review criteria. Of these, just 3 were rated as of moderate or high quality on AMSTAR-2, with the majority having critical flaws: only a third reported registering a protocol, and less than one in five searched named COVID-19 databases. Review conduct and publication were rapid, with 52 of the 88 systematic reviews reported as being conducted within 3 weeks, and a half published within 3 weeks of submission. Researcher and media interest, as measured by altmetrics and citations, was high, and was not correlated with quality. DISCUSSION: This meta-research of early published COVID-19 evidence syntheses found low-quality reviews being published at pace, often with short publication turnarounds. Despite being of low quality and many lacking robust methods, the reviews received substantial attention across both academic and public platforms, and the attention was not related to the quality of review methods. INTERPRETATION: Flaws in systematic review methods limit the validity of a review and the generalisability of its findings. Yet, by being reported as 'systematic reviews', many readers may well regard them as high-quality evidence, irrespective of the actual methods undertaken. The challenge especially in times such as this pandemic is to provide indications of trustworthiness in evidence that is available in 'real time'. PROSPERO REGISTRATION NUMBER: CRD42020188822.

Impact of COVID-19 and other infectious conditions requiring isolation on the provision of and adaptations to fundamental nursing care in hospital in terms of overall patient experience, care quality, functional ability, and treatment outcomes: systematic review.

AIM: This systematic review identifies, appraises and synthesizes the evidence on the provision of fundamental nursing care to hospitalized patients with a highly infectious virus and the effectiveness of adaptations to overcome barriers to care. DESIGN: Systematic review. DATA SOURCES: In July 2020, we searched Medline, PsycINFO (OvidSP), CINAHL (EBSCOhost), BNI (ProQuest), WHO COVID-19 Database (https://search.bvsalud.org/) MedRxiv (https://www.medrxiv.org/), bioRxiv (https://www.biorxiv.org/) and also Google Scholar, TRIP database and NICE Evidence, forwards citation searching and reference checking of included papers, from 2016 onwards. REVIEW METHODS: We included quantitative and qualitative research reporting (i) the views, perceptions and experiences of patients who have received fundamental nursing care whilst in hospital with COVID-19, MERS, SARS, H1N1 or EVD or (ii) the views, perceptions and experiences of professional nurses and non-professionally registered care workers who have provided that care. We included review articles, commentaries, protocols and guidance documents. One reviewer performed data extraction and quality appraisal and was checked by another person. RESULTS: Of 3086 references, we included 64 articles; 19 empirical research and 45 review articles, commentaries, protocols and guidance documents spanning five pandemics. Four main themes (and 11 sub-themes) were identified. Barriers to delivering fundamental care were wearing personal protective equipment, adequate staffing, infection control procedures and emotional challenges of care. These barriers were addressed by multiple adaptations to communication, organization of care, staff support and leadership. CONCLUSION: To prepare for continuation of the COVID-19 pandemic and future pandemics, evaluative studies of adaptations to fundamental healthcare delivery must be prioritized to enable evidence-based care to be provided in future. IMPACT: Our review identifies the barriers nurses experience in providing fundamental care during a pandemic, highlights potential adaptations that address barriers and ensure positive healthcare experiences and draws attention to the need for evaluative research on fundamental care practices during pandemics.

Multi-muscle deep learning segmentation to automate the quantification of muscle fat infiltration in cervical spine conditions.

Muscle fat infiltration (MFI) has been widely reported across cervical spine disorders. The quantification of MFI requires time-consuming and rater-dependent manual segmentation techniques. A convolutional neural network (CNN) model was trained to segment seven cervical spine muscle groups (left and right muscles segmented separately, 14 muscles total) from Dixon MRI scans (n = 17, 17 scans < 2 weeks post motor vehicle collision (MVC), and 17 scans 12 months post MVC). The CNN MFI measures demonstrated high test reliability and accuracy in an independent testing dataset (n = 18, 9 scans < 2 weeks post MVC, and 9 scans 12 months post MVC). Using the CNN in 84 participants with scans < 2 weeks post MVC (61 females, 23 males, age = 34.2 ± 10.7 years) differences in MFI between the muscle groups and relationships between MFI and sex, age, and body mass index (BMI) were explored. Averaging across all muscles, females had significantly higher MFI than males (p = 0.026). The deep cervical muscles demonstrated significantly greater MFI than the more superficial muscles (p < 0.001), and only MFI within the deep cervical muscles was moderately correlated to age (r > 0.300, p ≤ 0.001). CNN's allow for the accurate and rapid, quantitative assessment of the composition of the architecturally complex muscles traversing the cervical spine. Acknowledging the wider reports of MFI in cervical spine disorders and the time required to manually segment the individual muscles, this CNN may have diagnostic, prognostic, and predictive value in disorders of the cervical spine.

Erratum: Novel high-affinity EGFRvIII-specific chimeric antigen receptor T cells effectively eliminate human glioblastoma.

[This corrects the article DOI: 10.1002/cti2.1283.].

Meta-ethnography of the purpose of meaningful occupation for people living with dementia.

BACKGROUND: Guidance on provision of care for people with dementia states that occupation people find meaningful is essential for well-being; however, definitions of 'meaningful occupation' are often broad, with intrinsic meaning coming from within the person rather than the activity, leading to an inconsistent understanding of its purpose. OBJECTIVES: This study aimed to create a conceptual framework depicting the types of meaning that are seen as stemming from occupation. METHOD: Six electronic databases were searched (CINAHL, PubMed Central, PsycINFO, Embase, AMED, ASSIA) using a pre-specified search strategy to identify qualitative studies relating to meaningful occupation for people living with dementia. From 114 eligible full-text articles, six qualitative studies were identified as sufficiently rich, topically relevant and explicit in their definition of meaningful activity. A further 14 were purposefully sampled for their ability to refute or advance the emerging conceptual framework. The synthesis is based on meta-ethnography and is reported following eMERGe guidance. RESULTS: We found the fundamental purpose of occupation is to support the person living with dementia to feel they are living a meaningful and fulfilling life. Three overlapping concepts were identified: (i) catalytic environment, (ii) meaningful life and (iii) occupation as a tool. CONCLUSION: The framework proposes how occupation could support meaning in multiple ways and considers how these forms of meaning were influenced by the worldviews and values of the individual, and context in which they were experienced. IMPLICATIONS FOR PRACTICE: The conceptual framework offers a consistent theoretical grounding with which to measure effectiveness of meaningful occupation for people living with dementia.