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EBioMedicine Jan 2024Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction globally. Associated neurological symptoms and signs have historically...
BACKGROUND
Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction globally. Associated neurological symptoms and signs have historically been explained by pathobiology within the cervical spine. However, recent advances in imaging have shed light on numerous brain changes in patients with DCM, and it is hypothesised that these changes contribute to DCM pathogenesis. The aetiology, significance, and distribution of these supraspinal changes is currently unknown. The objective was therefore to synthesise all current evidence on brain changes in DCM.
METHODS
A systematic review was performed. Cross-sectional and longitudinal studies with magnetic resonance imaging on a cohort of patients with DCM were eligible. PRISMA guidelines were followed. MEDLINE and Embase were searched to 28th August 2023. Duplicate title/abstract screening, data extraction and risk of bias assessments were conducted. A qualitative synthesis of the literature is presented as per the Synthesis Without Meta-Analysis (SWiM) reporting guideline. The review was registered with PROSPERO (ID: CRD42022298538).
FINDINGS
Of the 2014 studies that were screened, 47 studies were identified that used MRI to investigate brain changes in DCM. In total, 1500 patients with DCM were included in the synthesis, with a mean age of 53 years. Brain alterations on MRI were associated with DCM both before and after surgery, particularly within the sensorimotor network, visual network, default mode network, thalamus and cerebellum. Associations were commonly reported between brain MRI alterations and clinical measures, particularly the Japanese orthopaedic association (JOA) score. Risk of bias of included studies was low to moderate.
INTERPRETATION
The rapidly expanding literature provides mounting evidence for brain changes in DCM. We have identified key structures and pathways that are altered, although there remains uncertainty regarding the directionality and clinical significance of these changes. Future studies with greater sample sizes, more detailed phenotyping and longer follow-up are now needed.
FUNDING
ODM is supported by an Academic Clinical Fellowship at the University of Cambridge. BMD is supported by an NIHR Clinical Doctoral Fellowship at the University of Cambridge (NIHR300696). VFJN is supported by an NIHR Rosetrees Trust Advanced Fellowship (NIHR302544). This project was supported by an award from the Rosetrees Foundation with the Storygate Trust (A2844).
Topics: Humans; Middle Aged; Brain; Cross-Sectional Studies; Magnetic Resonance Imaging; Spinal Cord Diseases
PubMed: 38113760
DOI: 10.1016/j.ebiom.2023.104915 -
The Cochrane Database of Systematic... Nov 2023Postpartum haemorrhage (PPH), defined as blood loss of 500 mL or more after childbirth, is the leading cause of maternal mortality worldwide. It is possible to prevent... (Review)
Review
BACKGROUND
Postpartum haemorrhage (PPH), defined as blood loss of 500 mL or more after childbirth, is the leading cause of maternal mortality worldwide. It is possible to prevent complications of PPH with timely and appropriate detection and management. However, implementing the best methods of PPH prevention, detection and management can be challenging, particularly in low- and middle-income countries.
OBJECTIVES
Our overall objective was to explore the perceptions and experiences of women, community members, lay health workers, and skilled healthcare providers who have experience with PPH or with preventing, detecting, and managing PPH, in community or health facility settings.
SEARCH METHODS
We searched MEDLINE, CINAHL, Scopus, and grey literature on 13 November 2022 with no language restrictions. We then performed reference checking and forward citation searching of the included studies.
SELECTION CRITERIA
We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored perceptions and experiences of PPH prevention, detection, and management among women, community members, traditional birth attendants, healthcare providers, and managers.
DATA COLLECTION AND ANALYSIS
We used three-stage maximum variation sampling to ensure diversity in terms of relevance of the study to the review objectives, richness of data, and coverage of critical contextual elements: setting (region, country income level), perspective (type of participant), and topic (prevention, detection, management). We extracted data using a data extraction form designed for this review. We used thematic synthesis to analyse and synthesise the evidence, and we used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. To identify factors that may influence intervention implementation, we mapped each review finding to the Theoretical Domains Framework (TDF) and the Capability, Motivation, and Opportunity model of Behaviour change (COM-B). We used the Behaviour Change Wheel to explore implications for practice.
MAIN RESULTS
We included 67 studies and sampled 43 studies for our analysis. Most were from low- or middle-income countries (33 studies), and most included the perspectives of women and health workers. We downgraded our confidence in several findings from high confidence to moderate, low, or very-low confidence, mainly due to concerns about how the studies were conducted (methodological limitations) or concerns about missing important perspectives from some types of participants or in some settings (relevance). In many communities, bleeding during and after childbirth is considered "normal" and necessary to expel "impurities" and restore and cleanse the woman's body after pregnancy and birth (moderate confidence). In some communities, people have misconceptions about causes of PPH or believe that PPH is caused by supernatural powers or evil spirits that punish women for ignoring or disobeying social rules or for past mistakes (high confidence). For women who give birth at home or in the community, female family members or traditional birth attendants are the first to recognise excess bleeding after birth (high confidence). Family members typically take the decision of whether and when to seek care if PPH is suspected, and these family members are often influenced by trusted traditional birth attendants or community midwives (high confidence). If PPH is identified for women birthing at home or in the community, decision-making about the subsequent referral and care pathway can be multifaceted and complex (high confidence). First responders to PPH are not always skilled or trained healthcare providers (high confidence). In health facilities, midwives may consider it easy to implement visual estimation of blood loss with a kidney dish or under-pad, but difficult to accurately interpret the amount of blood loss (very low confidence). Quantifying (rather than estimating) blood loss may be a complex and contentious change of practice for health workers (low confidence). Women who gave birth in health facilities and experienced PPH described it as painful, embarrassing, and traumatic. Partners or other family members also found the experience stressful. While some women were dissatisfied with their level of involvement in decision-making for PPH management, others felt health workers were best placed to make decisions (moderate confidence). Inconsistent availability of resources (drugs, medical supplies, blood) causes delays in the timely management of PPH (high confidence). There is limited availability of misoprostol in the community owing to stockouts, poor supply systems, and the difficulty of navigating misoprostol procurement for community health workers (moderate confidence). Health workers described working on the maternity ward as stressful and intense due to short staffing, long shifts, and the unpredictability of emergencies. Exhausted and overwhelmed staff may be unable to appropriately monitor all women, particularly when multiple women are giving birth simultaneously or on the floor of the health facility; this could lead to delays in detecting PPH (moderate confidence). Inadequate staffing, high turnover of skilled health workers, and appointment of lower-level cadres of health workers are key challenges to the provision of quality PPH care (high confidence). Through team-based simulation training, health workers of different cadres (doctors, midwives, lay health workers) can develop a shared mental model to help them work quickly, efficiently, and amicably as a team when managing women with PPH (moderate confidence).
AUTHORS' CONCLUSIONS
Our findings highlight how improving PPH prevention, detection, and management is underpinned by a complex system of interacting roles and behaviours (community, women, health workers of different types and with different experiences). Multiple individual, sociocultural, and environmental factors influence the decisions and behaviours of women, families, communities, health workers, and managers. It is crucial to consider the broader health and social systems when designing and implementing PPH interventions to change or influence these behaviours. We have developed a set of prompts that may help programme managers, policymakers, researchers, and other key stakeholders to identify and address factors that affect implementation and scale-up of interventions to improve PPH prevention, detection, and management.
Topics: Pregnancy; Female; Humans; Postpartum Hemorrhage; Misoprostol; Health Personnel; Midwifery; Family
PubMed: 38009552
DOI: 10.1002/14651858.CD013795.pub2 -
Frontiers in Bioscience (Landmark... Oct 2023The retina, a component of the central nervous system, is composed of six distinct neuronal types and various types of glial cells. A technique for single-cell... (Review)
Review
The retina, a component of the central nervous system, is composed of six distinct neuronal types and various types of glial cells. A technique for single-cell transcriptome analysis called single-cell RNA sequencing (scRNA-seq) can be employed to study the complicated dynamics of several types of retinal cells. It meticulously examines how various cell types express their genes, shedding light on all biological processes. scRNA-seq is an alternative to regular RNA-seq, which cannot identify cellular heterogeneity. Understanding retinal diseases requires research on retinal cell heterogeneity. The identification of novel cell subpopulations can provide information about disease occurrence and progression as well as the specific biological functions of particular cells. We currently have a better understanding of the interactions among the brain, the retina, and its visual pathways thanks to the use of scRNA-seq to examine retinal development and disease pathogenesis. Additionally, this technology offers fresh perspectives on the sensitivity and molecular basis of cell subtypes linked to retinal diseases. Thanks to scRNA-seq technology, we now have a better understanding of the most recent developments and difficulties in retinal development and disorders. We believe that scRNA-seq is an important tool for developing cutting-edge treatments for retinal diseases. This paper presents a systematic review of the history of sRNA-seq technology development and provides an overview of the unique subtypes of retinal cells and the specific gene markers this technology identifies.
Topics: Humans; Retina; Neurons; Sequence Analysis, RNA; Retinal Diseases; Biology; Gene Expression Profiling
PubMed: 37919055
DOI: 10.31083/j.fbl2810247 -
Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
Biomedicine & Pharmacotherapy =... Nov 2023Humans rely on vision as their most important sense. This is accomplished by photoreceptors (PRs) in the retina that detect light but cannot function without the support... (Review)
Review
Humans rely on vision as their most important sense. This is accomplished by photoreceptors (PRs) in the retina that detect light but cannot function without the support and maintenance of the retinal pigment epithelium (RPE). In subretinal hemorrhage (SRH), blood accumulates between the neurosensory retina and the RPE or between the RPE and the choroid. Blood breakdown products subsequently damage PRs and the RPE and lead to poor vision and blindness. Hence, there is a high need for options to preserve the retina and visual functions. We conducted a systematic review of the literature in accordance with the PRISMA guidelines to identify the cell death mechanisms in RPE and PRs after SRH to deepen our understanding of the pathways involved. After screening 736 publications published until November 8, 2022, we identified 19 records that assessed cell death in PRs and/or RPE in experimental models of SRH. Among the different cell death mechanisms, apoptosis was the most widely investigated mechanism (11 records), followed by ferroptosis (4), whereas necroptosis, pyroptosis, and lysosome-dependent cell death were only assessed in one study each. We discuss different therapeutic options that were assessed in these studies, including the removal of the hematoma/iron chelation, cytoprotection, anti-inflammatory agents, and antioxidants. Further systematic investigations will be necessary to determine the exact cell death mechanisms after SRH with respect to different blood breakdown components, cell types, and time courses. This will form the basis for the development of novel treatment options for SRH.
Topics: Humans; Retinal Pigment Epithelium; Retina; Cell Death; Photoreceptor Cells; Hemorrhage
PubMed: 37742603
DOI: 10.1016/j.biopha.2023.115572 -
Neural Regeneration Research Nov 2023Amblyopia is the most common cause of vision loss in children and can persist into adulthood in the absence of effective intervention. Previous clinical and neuroimaging...
Amblyopia is the most common cause of vision loss in children and can persist into adulthood in the absence of effective intervention. Previous clinical and neuroimaging studies have suggested that the neural mechanisms underlying strabismic amblyopia and anisometropic amblyopia may be different. Therefore, we performed a systematic review of magnetic resonance imaging studies investigating brain alterations in patients with these two subtypes of amblyopia; this study is registered with PROSPERO (registration ID: CRD42022349191). We searched three online databases (PubMed, EMBASE, and Web of Science) from inception to April 1, 2022; 39 studies with 633 patients (324 patients with anisometropic amblyopia and 309 patients with strabismic amblyopia) and 580 healthy controls met the inclusion criteria (e.g., case-control designed, peer-reviewed articles) and were included in this review. These studies highlighted that both strabismic amblyopia and anisometropic amblyopia patients showed reduced activation and distorted topological cortical activated maps in the striate and extrastriate cortices during task-based functional magnetic resonance imaging with spatial-frequency stimulus and retinotopic representations, respectively; these may have arisen from abnormal visual experiences. Compensations for amblyopia that are reflected in enhanced spontaneous brain function have been reported in the early visual cortices in the resting state, as well as reduced functional connectivity in the dorsal pathway and structural connections in the ventral pathway in both anisometropic amblyopia and strabismic amblyopia patients. The shared dysfunction of anisometropic amblyopia and strabismic amblyopia patients, relative to controls, is also characterized by reduced spontaneous brain activity in the oculomotor cortex, mainly involving the frontal and parietal eye fields and the cerebellum; this may underlie the neural mechanisms of fixation instability and anomalous saccades in amblyopia. With regards to specific alterations of the two forms of amblyopia, anisometropic amblyopia patients suffer more microstructural impairments in the precortical pathway than strabismic amblyopia patients, as reflected by diffusion tensor imaging, and more significant dysfunction and structural loss in the ventral pathway. Strabismic amblyopia patients experience more attenuation of activation in the extrastriate cortex than in the striate cortex when compared to anisometropic amblyopia patients. Finally, brain structural magnetic resonance imaging alterations tend to be lateralized in the adult anisometropic amblyopia patients, and the patterns of brain alterations are more limited in amblyopic adults than in children. In conclusion, magnetic resonance imaging studies provide important insights into the brain alterations underlying the pathophysiology of amblyopia and demonstrate common and specific alterations in anisometropic amblyopia and strabismic amblyopia patients; these alterations may improve our understanding of the neural mechanisms underlying amblyopia.
PubMed: 37282452
DOI: 10.4103/1673-5374.371349 -
Eye (London, England) Oct 2023To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support... (Review)
Review
OBJECTIVE
To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.
METHODS
We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).
RESULTS
From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.
CONCLUSION
There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.
Topics: Humans; Adult; Quality of Life; Reproducibility of Results; Optic Neuritis; Surveys and Questionnaires; Patient Reported Outcome Measures; Multiple Sclerosis
PubMed: 36932161
DOI: 10.1038/s41433-023-02478-z -
Survey of Ophthalmology 2024Among ocular infections, trachoma is the main cause of blindness. Repeated conjunctival Chlamydia trachomatis infections lead to trichiasis, corneal opacification, and... (Review)
Review
Among ocular infections, trachoma is the main cause of blindness. Repeated conjunctival Chlamydia trachomatis infections lead to trichiasis, corneal opacification, and visual impairment. Surgery is often needed to relieve discomfort and preserve vision; however, a high postoperative trachomatous trichiasis (PTT) rate has been observed in various settings. We wanted to know why, whether PTT rates could be reduced, and how to manage the PTT that occurs. We performed a search of the literature. Of 217 papers screened, 59 studies were identified for inclusion as potentially relevant, the majority having been excluded for not directly concerning PTT in humans. Preventing PTT is a major challenge. Only one published trial, the STAR trial in Ethiopia, has reported a cumulative PTT rate <10% one year after surgery. The literature on the management of PTT is sparse. Though no PTT management guidelines are available, high-quality surgery with a low rate of unfavorable outcomes for PTT patients is likely to require enhanced training of a smaller group of highly-skilled surgeons. Based on the surgical complexity and the authors' own experience, the pathway for patients suffering from PTT should be studied further for improvement.
Topics: Humans; Trachoma; Trichiasis; Conjunctiva; Blindness; Vision, Low
PubMed: 36878359
DOI: 10.1016/j.survophthal.2023.02.008 -
Eye (London, England) Jul 2023Cerebral Visual Impairment (CVI) is a common condition in the UK. Patients with conditions associated with CVI are frequently seen in paediatric ophthalmology clinics... (Review)
Review
Cerebral Visual Impairment (CVI) is a common condition in the UK. Patients with conditions associated with CVI are frequently seen in paediatric ophthalmology clinics offering eye care professionals an opportunity to identify children proactively. In most cases CVI occurs as part of a neurodevelopmental condition or as a feature of multiple and complex disabilities. However, CVI can also be seen in children with apparently typical development. In some cases, high contrast visual acuity is normal and in other cases severely impaired. As such, identification of CVI requires evaluation of aspects of visual performance beyond high contrast acuity and consideration that visual function of those with CVI may fluctuate. Few paediatric ophthalmologists have received formal training in CVI. The detection and diagnosis of CVI varies across the UK and patients report hugely different experiences. A diagnosis of CVI is made based on professional clinical judgement and it is recognised that individual perspectives and local practice in the specific methodologies of assessment will vary. A systematic review and survey of professionals is underway to attempt to reach agreement on diagnostic criteria. Nonetheless, established pathways and published protocols can offer guidance on how a paediatric ophthalmology service can approach assessment of the child with suspected CVI. The purpose of this paper is to present a summary of research and clinical practice methods for detecting and diagnosing CVI in a paediatric ophthalmology outpatient setting. It represents current understanding of the topic and acknowledges the evolving nature of both practice and the evidence-base. A rapid literature review was undertaken to identify articles relating to clinical investigation of children with CVI. A focus group of QTVI and subject matter experts from sight loss charities was undertaken to address areas which were not covered by the literature review.
Topics: Child; Humans; Consensus; Vision Disorders; Visual Acuity; Ophthalmology; Blindness
PubMed: 36258009
DOI: 10.1038/s41433-022-02261-6